By: Cobey Bartels

Date: 16.03.2020

Friend of Owner//Driver and owner of the iconic Filthy White 4000 we covered last year, Mick Moo Lake, was diagnosed with cancer on Christmas Eve.

Mick and Mel Lake, with 'Filthy'

Since the devastating news, Mick and his wife Mel have been struggling to balance treatment and operating their business Truckin Stainless setting up a GoFundMe page to help cover the costs of hospital care.

Mick has Double Myeloma, a form of cancer that develops from plasma cells in the bone marrow, and has been receiving ongoing treatment since New Years Eve.

In 10 weeks Mick is having a Stem Cell Blood Transfusion, which will put him out of work for at least a month and will put significant strain on his business and familys livelihood.

At the time of writing, the GoFundMe page has raised $3,195 and Mick and Mel say the money will go towards covering the cost of treatment and help keep their business afloat.

Mick has been working through the treatment, where possible, to keep Truckin Stainless kicking along with the help of his good mate Steve who travelled down from Mackay to help lighten the load.

"He heard about what was going on when he was down here at the time, and he decided to stay and help while I was getting treatment," Mick says.

"Ive been working through it, going to hospital for treatments then back to the workshop - i havent stopped.

"In respect of all the wonderful people that have had to endure this terrible disease, we understand that asking for donations seems a bit steep, but if you would like to donate please do so, or think to donate to any cancer foundation," he says.

You can donate or find out more HERE.

You can also follow our updates by liking us on Facebook.

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Moo trucks on through cancer battle - Owner//Driver

Bone Marrow Stem Cells Comments Off on Moo trucks on through cancer battle – Owner//Driver | March 16th, 2020

Immune cells by fluorescence microscopy: Blood stem cells remember a previous attack and produce more immune cells like these macrophages to fight a new infection. Credit: Sieweke lab/CIML

These findings should have a significant impact on future vaccination strategies and pave the way for new treatments of an underperforming or over-reacting immune system. The results of this research are published in Cell Stem Cell on March 12, 2020.

Stem cells in our bodies act as reservoirs of cells that divide to produce new stem cells, as well as a myriad of different types of specialized cells, required to secure tissue renewal and function. Commonly called blood stem cells, the hematopoietic stem cells (HSC) are nestled in the bone marrow, the soft tissue that is in the center of large bones such as the hips or thighs. Their role is to renew the repertoire of blood cells, including cells of the immune system which are crucial to fight infections and other diseases.

Until a decade ago, the dogma was that HSCs were unspecialized cells, blind to external signals such as infections. Only their specialized daughter cells would sense these signals and activate an immune response. But work from Prof. Michael Siewekes laboratory and others over the past years has proven this dogma wrong and shown that HSCs can actually sense external factors to specifically produce subtypes of immune cells on demand to fight an infection. Beyond their role in an emergency immune response, the question remained as to the function of HSCs in responding to repeated infectious episodes. The immune system is known to have a memory that allows it to better respond to returning infectious agents. The present study now establishes a central role for blood stem cells in this memory.

We discovered that HSCs could drive a more rapid and efficient immune response if they had previously been exposed to LPS, a bacterial molecule that mimics infection, said Dr. Sandrine Sarrazin, Inserm researcher and senior-author of the publication. Prof. Michael Sieweke, Humboldt Professor at TU Dresden, CNRS Research Director and last author of the publication, explained how they found the memory was stored within the cells: The first exposure to LPS causes marks to be deposited on the DNA of the stem cells, right around genes that are important for an immune response. Much like bookmarks, the marks on the DNA ensure that these genes are easily found, accessible and activated for a rapid response if a second infection by a similar agent was to come.

The authors further explored how the memory was inscribed on the DNA, and found C/EBP? to be the major actor, describing a new function for this factor, which is also important for emergency immune responses. Together, these findings should lead to improvements in tuning the immune system or better vaccination strategies.

The ability of the immune system to keep track of previous infections and respond more efficiently the second time they are encountered is the founding principle of vaccines. Now that we understand how blood stem cells bookmark immune response circuits, we should be able to optimize immunization strategies to broaden the protection to infectious agents. It could also more generally lead to new ways to boost the immune response when it underperforms or turn it off when it overreacts, concluded Prof. Michael Sieweke.

The research group of Prof. Michael Sieweke works at the interface of immunology and stem cell research. The scientists focus on the study of hematopoietic stem cells and macrophages, long-lived mature cells of the immune system that fulfil an important role in tissue regeneration. In 2018, Prof. Michael Sieweke received the most valuable research award in Germany: the Alexander von Humboldt Professorship, which brings top international researchers to German universities. In addition to his position as Research Director at the Centre for Immunology at the University of Marseille Luminy, he now acts as Deputy Director at the Center for Regenerative Therapies at TU Dresden (CRTD). CRTD is academic home for scientists from more than 30 nations. Their mission is to discover the principles of cell and tissue regeneration and leveraging this for recognition, treatment and reversal of diseases. The CRTD links the bench to the clinic, scientists to clinicians to pool expertise in stem cells, developmental biology, gene-editing and regeneration towards innovative therapies for neurodegenerative diseases such as Alzheimers and Parkinsons disease, hematological diseases such as leukaemia, metabolic diseases such as diabetes, retina and bone diseases.

Reference: C/EBP-Dependent Epigenetic Memory Induces Trained Immunity in Hematopoietic Stem Cells by Brengre de Laval, Julien Maurizio, Prashanth K. Kandalla, Gabriel Brisou, Louise Simonnet, Caroline Huber, Gregory Gimenez, Orit Matcovitch-Natan, Susanne Reinhardt, Eyal David, Alexander Mildner, Achim Leutz, Bertrand Nadel, Christophe Bordi, Ido Amit, Sandrine Sarrazin and Michael H.Sieweke, 12 March 2020, Cell Stem Cell.DOI: 10.1016/j.stem.2020.01.017

This study was funded by TU Dresden / CRTD through the German Excellence Initiative, the German Research Foundation as well as through an ERC Advanced Grant from the European Research Council and the Alexander von Humboldt Foundation. The study was further supported by funding from the Institut National de la Sante et de la Recherche Medicale, the Centre National de la Recherche Scientifique, Aix-Marseille University, the Agence Nationale de la Recherche, the Foundation ARC pour la Recherche sur le Cancer, an INSERM-Helmholtz cooperation programme and the Einstein Foundation.

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Newly Discovered Memory in Our Bones: Keeping a Record of Previous Infections to Boost Immunity - SciTechDaily

Bone Marrow Stem Cells Comments Off on Newly Discovered Memory in Our Bones: Keeping a Record of Previous Infections to Boost Immunity – SciTechDaily | March 15th, 2020

Revolutionary Gene-Editing Tool

Cardiovascular or heart disease (CVDs) is the leading cause of death across the world. Heart attacks resulting due to CVDs can cause death, and severe damage to cardiac muscle a muscle that forms the wall of the heart in survivors. However, researchers claim that they have discovered stem-cell activated mechanisms that promote healing after a heart attack.

According to the study by researchers from Mayo Clinic, stem cells were found to reverse the damage and restore cardiac muscle back to its condition before a heart attack. Human cardiopoietic cells obtained from stem cells within the bone marrow were found to hone in on damaged proteins and reverse intricate changes that a heart attack caused.

"The response of the diseased heart to cardiopoietic stem cell treatment revealed development and growth of new blood vessels, along with new heart tissue," said Dr. Kent Arrell, first author of the study, in a statement.

For the study, the researchers examined the diseased hearts of mice. The hearts of mice that received human cardiopoietic stem cell therapy were compared with those of that did not. Nearly 4,000 cardiac proteins were identified using a data science technique to map proteins found in the cardiac muscle. Over 10 per cent of the discovered proteins were found to suffer damage as a result of a heart attack.

"While we anticipated that the stem cell treatment would produce a beneficial outcome, we were surprised how far it shifted the state of diseased hearts away from disease and back toward a healthy, pre-disease state," said Dr. Arrell.

While the organs in the human body have the ability to repair their damaged cells, they may be unable to restore the loss entirely, and this holds good for cardiac cells as well. Dr. Andre Terzic, senior author of the study, said: "The extent of change caused by a heart attack is too great for the heart to repair itself or to prevent further damage from occurring."

He explained that upon the administration of cardiopoietic stem cell therapy to mice, a partial or complete reversal of nearly two-thirds of the damage caused by a heart attack was noted. Around 85 per cent of all cellular functional categories struck by the disease responded favorably to the treatment.

According to the World Health Organisation (WHO), CVDs claim nearly 18 million lives every year, which translates to 31 per cent of all deaths. The findings of the study provide an improved understanding of the restoration of heart health using stem cells and provide a framework for wider utilization of stem cell therapy for the treatment of various conditions.

Stressing that the actual mechanism behind the repair of diseased organs by stem cells is poorly understood, Dr. Terzic added: "This study sheds light on the most intimate, yet comprehensive, regenerative mechanisms paving a road map for responsible and increasingly informed stem cell application."

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Stem cells can reverse damage caused by heart attack; repair mechanism discovered: Study - International Business Times, Singapore Edition

Bone Marrow Stem Cells Comments Off on Stem cells can reverse damage caused by heart attack; repair mechanism discovered: Study – International Business Times, Singapore Edition | March 15th, 2020

A 40-year-old HIV patient has been declared cured after a promising treatment has left him with no active virus. The man, Adam Castillejo, was the subject of extensive research in early 2019 after doctors failed to find HIV in his body over an 18-month period after previously being diagnosed in 2003.

Castillejo, known by the nickname London Patient lived with the disease for many years, taking medicine to manage it since 2012. That same year he was diagnosed with Hodgkins Lymphoma and later endured a bone marrow transplant. That operation may have ultimately cured him of HIV and appears to have made him only the second person to ever be cured of the disease that causes AIDS.

As ScienceAlert reports, the bone marrow transplant that doctors performed on Castillejo used cells from a donor with a very special genetic quirk. The cells are thought to work against HIV in the body, but there was no guarantee that the transplant would provide any concrete benefits beyond treating the cancer.

However, it appears as though the decision to treat Castillejo with the unique stem cells worked in more ways than one and last year doctors announced they couldnt find the virus in his body after 18 months. At the time, they were hesitant to declare the London Patient cured, but after a new round of testing returned the same results, they are more confident that the active form of the virus has indeed been defeated.

This is a unique position to be in, a unique and very humbling position, Castillejo told the New York Times. I want to be an ambassador of hope.

While this sounds like incredible news and for Castillejo, it certainly is the treatment is not an option for everyone. With cancer limiting their options, doctors used the stem cell transplant as a last resort to keep him alive. Its a serious operation and one that was only performed because Castillejos condition was so dire.

Castillejo and the other HIV patient who had similar results, known as the Berlin Patient, may be uniquely fortunate. The doctors note that there are others who have had the same transplant performed but did not improve as rapidly as the others. There are obviously many factors at work here and as exciting as it is to see a second person cured of this terrible disease, theres a lot more work to be done before we can say HIV has been truly beaten.

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HIV patient appears to be cured after stem cell treatment - New York Post

Bone Marrow Stem Cells Comments Off on HIV patient appears to be cured after stem cell treatment – New York Post | March 13th, 2020

Although most of the news from the world of health and medicine has been quite bleak lately, there are still major strides being made in the sector in an effort to combat the worst illnesses that plague humankind. One such stride was just announced, and its certainly worth celebrating: A second person has been cured of HIV.

In a study published in the medical journal, The Lancet, which comes via Medical News Daily, researchers in London say theyve been able to cure a patient of HIV; meaning the patient tested negative for HIV for an extended period of time (30 months as of March, 2020) despite the lack of antiretroviral therapy.

The person whos been cured, Adam Castillejo, was formerly known only as the London patient in order to protect his identity. But Castillejo, who lives in London, came forward recently, and said that he aims to be an ambassador of hope.

The first person to be cured of HIV, Timothy Ray Brown, an American known originally as the Berlin patient, revealed his identity in 2010, saying that I wanted to do what I could to make [a cure] possible. My first step was releasing my name and image to the public. Brown lived and was treated in Berlin. Incidentally, he is technically the second Berlin patient because the results from treatment of the first one are debatable.

AIDS Policy Project with Timothy Ray Brown (third from left with sunglasses). Griffin Boyce.

Castillejo, as well as Brown, were cured of HIV not by antiretroviral medications, which are often able to drastically mitigate the effects, and transmission rate of, HIV, but rather by stem cell transplants from donor bone marrow. Both Castillejo and Brown hadand may still have, that is unclearcancer along with HIV, and were treated with the stem cell transplants primarily to tackle the former disease. (It seems in Castillejos case doctors and researchers were hoping to cure both simultaneously.)

Both Brown and Castillejo underwent a procedure known as a Hematopoietic stem cell transplantation (or HSCT), which involves injecting bone marrow stem cells from a donor, whos often times a parent or sibling, into the recipients bloodstream. Castillejos HSCT treatment was different from Browns, as well as many others, because it was performed with cells that expressed the CCR5 gene.

A video from the MD Anderson Cancer Center that gives a brief outline of how bone marrow stem cell transplants work.

In Castillejos case, stem cells with genomes that express the CCR5 gene were selected because of the fact that it allows for the production of the CCR5 protein: a protein that makes people far more resistant to HIV-1, which accounts for the vast majority of global HIV infections.

While Castillejo received stem cells that did express the CCR5 gene, Brown did notat least according to the study in The Lancet. In fact, according to a 2017 article in New Scientist (which says that Brown received cells with a mutated CCR5 gene, rather than an unexpressed CCR5 gene), some experts believe the curing of Browns HIV was actually due to a potential side effect of his procedure, known as graft-versus-host disease. According to New Scientist, these experts believe that the donor cells attacked Browns native, HIV-infected immune cells, subsequently killing off the virus.

In Castillejos case, on the other hand, it seems there was no graft-versus-host issue that could account for his diminishment of HIV infection levels beyond whats expected to be detectable. Instead, the authors of the study say that one of the implications here is that the Long-term remission of HIV-1 can be achieved utilizing these kinds of cells. The authors also say this method does not require total body irradiation, which would usually be required in cases like these to weaken a recipients immune system in order to allow them to accept donor cells.

An HIV-infected T cell. NIAID

Unfortunately, it seems the treatment that cured Castillejo of HIV is a nonstarter when it comes to mass deployment. There are fatal side effects associated with HSCT, with host-versus-graft chief among them, and doctors say that it should only be performed when there are no other options left.

Prof. Ravindra Kumar Gupta from the University of Cambridge in the U.K., the lead author of the study, told Medical News Daily that [Its] important to note that this curative treatment is high risk and only used as a last resort for patients with HIV who also have life threatening hematological [blood] malignancies.

But Gupta and the other authors of the study still appear to be optimistic that this stands as a proof-of-concept for the idea of using CCR5 gene editing to cure HIV on a larger scale. They warn in their study, however, that several barriers, including the need for increased gene editing efficiency and a lack of robust safety data, still stand in the way of something that could be used as a scalable strategy for tackling HIV.

What do you think about this method of treating HIV? Do you think gene editing will play a big role in curing HIV, or do you think there are other, more promising treatments worth pursuing instead? Let us know your thoughts in the comments.

Feature image: C. Goldsmith / Eliot Lash

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A Second Person Has Been Cured of HIV - Nerdist

Bone Marrow Stem Cells Comments Off on A Second Person Has Been Cured of HIV – Nerdist | March 13th, 2020

Newswise The number of COVID-19 cases are expected to continue to grow across the globe in the upcoming months and that means more people will have to take extra measures to help protect themselves and reduce the transmission of the disease. This is particularly important for people with cancer, whose immune systems have often been weakened by their cancer treatments.

But does that mean people with cancer should stockpile hand sanitizer and face masks?

Oncologists Gary Schiller, MD, and Joshua Sasine, MD, PhD, help explain what cancer patients need to know about COVID-19.

Dr. Schiller is a professor of hematology/oncology at the David Geffen School of Medicine at UCLA and director of the hematological malignancies/stem cell transplantation unit, and Dr. Sasine is an assistant professor of medicine and director of the CAR T cell program at the UCLA Jonsson Comprehensive Cancer Center.

Which cancer patients should be concerned about coronavirus?

Sasine: The patients most at risk are those with bone marrow cancers or who have had a bone marrow transplant within the last 12 months. If patients have cancer and are on active chemotherapy, they are also at a higher risk than the general population. This is especially true if they are over the age of 60.

Schiller: Bone marrow transplant recipients who received bone marrow from other people are the most immunocompromised patients we take care of and the group at greatest risk for sustaining a life-threatening complication from an infection.

What does it mean to have a compromised immune system?

Sasine: The body's white blood cells normally clear out infections, like bacteria, viruses, and fungi. When the cells have either decreased in number, function, or both, the immune system is compromised. This can be due to having cancer, HIV, getting chemotherapy, and many other situations. This means that a person is more likely than others to contract an infection and the infection is likely to do more harm than average. It might also last longer.

Are there precautions cancer patients should be taking?

Schiller: Patients who are immunocompromised need to be wary of going into crowds, should maintain good hand washing techniques and should stay away from individuals who have a cough.

Sasine: For most events, canceling plans is ideal. However, sometimes one must weigh the risks and benefits. If there is a very important event (son or daughter is getting married, etc.) this might be a risk worth taking.

Should cancer patients delay travel plans?

Schiller: For patients with malignancies of the blood and bone marrow, and patients who had bone marrow transplants, I absolutely tell them to delay travel. Dont travel right now.

Is it safe for patients to come to the hospital and clinics for treatment?

Schiller: Yes. Weve been working to develop better isolation procedures and policies to isolate the potentially sick patients from our immunocompromised patients. For example, bringing the potentially sick patients in through a different entrance to isolate them in the waiting room and put them in an isolation room for evaluation.

Should patients be wearing a mask or stockpile hand sanitizer?

Schiller: A mask is not sufficient protection and were concerned that if you wear a mask, especially one that is insufficiently protective, then you have a false sense of security and you may put yourself in a position that might compromise your safety. In regards to hand sanitizer, I would like my patients to stockpile on soap and water. That would be more effective than using hand sanitizer repeatedly.

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Cancer and COVID-19: What you should know - Newswise

Bone Marrow Stem Cells Comments Off on Cancer and COVID-19: What you should know – Newswise | March 13th, 2020

NEW YORK, March 10, 2020 (GLOBE NEWSWIRE) -- Mesoblast Limited(Nasdaq: MESO; ASX:MSB) today announced that it plans to evaluate its allogeneic mesenchymal stem cell (MSC) product candidate remestemcel-L in patients with acute respiratory distress syndrome (ARDS) caused by coronavirus (COVID-19) in the United States, Australia, China and Europe. The Company is in active discussions with various government and regulatory authorities, medical institutions and pharmaceutical companies to implement these activities.

Mortality in COVID-19 infected patients with the inflammatory lung condition acute respiratory distress syndrome (ARDS) is reported to approach 50%, and is associated with older age, co-morbidities such as diabetes, higher disease severity, and elevated markers of inflammation.1 Current therapeutic interventions do not appear to be improving in-hospital survival.1

Remestemcel-L has potential for use in the treatment of ARDS, which is the principal cause of death in COVID-19 infection.1 This is supported by recently published results from an investigator-initiated clinical study conducted in China which reported that allogeneic MSCs cured or significantly improved functional outcomes in all seven treated patients with severe COVID-19 pneumonia.2

Additionally, in post-hoc analyses of a 60-patient randomized controlled study in chronic obstructive pulmonary disease (COPD), remestemcel-L infusions were well tolerated, significantly reduced inflammatory biomarkers, and significantly improved pulmonary function in those patients with elevated inflammatory biomarkers. Since the same inflammatory biomarkers are also elevated in COVID-19, these data suggest that remestemcel-L could be useful in the treatment of patients with ARDS due to COVID-19.The COPD study results have been submitted for presentation at an international conference, with full results to be submitted for publication shortly.

Remestemcel-L is being studied in numerous clinical trials across several inflammatory conditions, including in elderly patients with lung disease and adults and children with steroid-refractory acute graft versus host disease (aGVHD).3-5 This product candidate is currently being reviewed by the United States Food and Drug Administration (FDA) for potential approval in the treatment of children with steroid-refractory aGVHD.

Remestemcel-L Remestemcel-L is being developed for rare pediatric and adult inflammatory conditions. It is an investigational therapy comprising culture-expanded MSCs derived from the bone marrow of an unrelated donor and is administered in a series of intravenous infusions. Remestemcel-L is believed to have immunomodulatory properties to counteract the inflammatory processes that are implicated in several diseases by down-regulating the production of pro-inflammatory cytokines, increasing production of anti-inflammatory cytokines, and enabling recruitment of naturally occurring anti-inflammatory cells to involved tissues.

Intellectual PropertyMesoblasts intellectual property (IP) portfolio encompasses over 1,000 patents or patent applications in all major markets and includes the use of MSCs obtained from any source for patients with acute respiratory distress syndrome (ARDS),and for inflammatory lung disease due to coronavirus (COVID-19), influenza and other viruses. Additionally, these patents cover Mesoblasts manufacturing processes that yield industrial-scale cellular medicines.This IP position is expected to provide Mesoblast with substantial commercial advantages as it develops its product candidates for these conditions.

References1. Liu Y et al. Clinical features and progression of acute respiratory distress syndrome in coronavirus disease 2019. Medrxiv 2020; https://doi.org/10.1101/2020.02.17.200241662. Leng Z, et al. Transplantation of ACE2- Mesenchymal Stem Cells Improves the Outcome of Patients with COVID-19 Pneumonia[J]. Aging and Disease, 10.14336/AD.2020.02283. Kurtzberg J et al. Annual Meeting of the American Society for Transplantation Cell Therapy, 2020.4. Chaudhury S et al. A Phase 3 Single-Arm, Prospective Study of Remestemcel-L, Ex-Vivo Cultured Adult Human Mesenchymal Stromal Cells, for the Treatment of Steroid Refractory Acute GVHD in Pediatric Patients. Biol Blood Marrow Transplant 2018; 24:S119S290.5. Kurtzberg J et al. Allogeneic human mesenchymal stem cell therapy (remestemcel-L, Prochymal) as a rescue agent for severe refractory acute graft-versus-host disease in pediatric patients. Biol Blood Marrow Transplant. 2014 Feb;20(2):229-35.

About MesoblastMesoblast Limited (Nasdaq: MESO; ASX: MSB) is a world leader in developing allogeneic (off-the-shelf) cellular medicines. The Company has leveraged its proprietary mesenchymal lineage cell therapy technology platform to establish a broad portfolio of commercial products and late-stage product candidates. Mesoblasts proprietary manufacturing processes yield industrial-scale, cryopreserved, off-the-shelf, cellular medicines. These cell therapies, with defined pharmaceutical release criteria, are planned to be readily available to patients worldwide.

Mesoblast has filed a Biologics License Application to the United States Food and Drug Administration (FDA) to seek approval of its product candidate RYONCIL (remestemcel-L) for steroid-refractory acute graft versus host disease (acute GvHD). Remestemcel-L is also being developed for other rare diseases. Mesoblast is completing Phase 3 trials for its product candidates for advanced heart failure and chronic low back pain. If approved, RYONCIL is expected to be launched in the United States in 2020 for pediatric steroid-refractory acute GVHD. Two products have been commercialized in Japan and Europe by Mesoblasts licensees, and the Company has established commercial partnerships in Europe and China for certain Phase 3 assets.

Mesoblast has locations in Australia, the United States and Singapore and is listed on the Australian Securities Exchange (MSB) and on the Nasdaq (MESO). For more information, please see http://www.mesoblast.com, LinkedIn: Mesoblast Limited and Twitter: @Mesoblast

Forward-Looking StatementsThis announcement includes forward-looking statements that relate to future events or our future financial performance and involve known and unknown risks, uncertainties and other factors that may cause our actual results, levels of activity, performance or achievements to differ materially from any future results, levels of activity, performance or achievements expressed or implied by these forward-looking statements. We make such forward-looking statements pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 and other federal securities laws. Forward-looking statements should not be read as a guarantee of future performance or results, and actual results may differ from the results anticipated in these forward-looking statements, and the differences may be material and adverse. Forward- looking statements include, but are not limited to, statements about: the initiation, timing, progress and results of Mesoblasts preclinical and clinical studies, and Mesoblasts research and development programs; Mesoblasts ability to advance product candidates into, enroll and successfully complete, clinical studies, including multi-national clinical trials; Mesoblasts ability to advance its manufacturing capabilities; the timing or likelihood of regulatory filings and approvals, manufacturing activities and product marketing activities, if any; the commercialization of Mesoblasts product candidates, if approved; regulatory or public perceptions and market acceptance surrounding the use of stem-cell based therapies; the potential for Mesoblasts product candidates, if any are approved, to be withdrawn from the market due to patient adverse events or deaths; the potential benefits of strategic collaboration agreements and Mesoblasts ability to enter into and maintain established strategic collaborations; Mesoblasts ability to establish and maintain intellectual property on its product candidates and Mesoblasts ability to successfully defend these in cases of alleged infringement; the scope of protection Mesoblast is able to establish and maintain for intellectual property rights covering its product candidates and technology; estimates of Mesoblasts expenses, future revenues, capital requirements and its needs for additional financing; Mesoblasts financial performance; developments relating to Mesoblasts competitors and industry; and the pricing and reimbursement of Mesoblasts product candidates, if approved. You should read this press release together with our risk factors, in our most recently filed reports with the SEC or on our website. Uncertainties and risks that may cause Mesoblasts actual results, performance or achievements to be materially different from those which may be expressed or implied by such statements, and accordingly, you should not place undue reliance on these forward-looking statements. We do not undertake any obligations to publicly update or revise any forward-looking statements, whether as a result of new information, future developments or otherwise.

Release authorized by the Chief Executive.

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Mesoblast To Evaluate Anti-Inflammatory Cell Therapy Remestemcel-L For Treatment Of COVID-19 Lung Disease - BioSpace

Bone Marrow Stem Cells Comments Off on Mesoblast To Evaluate Anti-Inflammatory Cell Therapy Remestemcel-L For Treatment Of COVID-19 Lung Disease – BioSpace | March 13th, 2020

Genes may determine what characteristics are passed down from parent to offspring, but each cell expresses these genes differently based on external epigenetic modifications. Epigenetics dont alter the gene sequence (genotype), but they do influence cell behavior and function (phenotype). The study of epigenetics helps us understand how phenotypic changes lead to disease, stem cell differentiation, and essentially, what drives the fate of every cell in the human body.The epigenome is not consistent between cells, or even between cells of the same type. Individual modifications come and go throughout a cells lifetime. Therefore, scientists are faced with the steep challenge as they try to decipher the role of epigenetics in disease and development.[i] Understanding intercellular heterogeneity is key here. The epigenome must be examined at single-cell resolution.

Now, with the advancement of single-cell sequencing methods like the single-cell assay for transposase accessible chromatin (scATAC-seq), researchers have access to sophisticated techniques to map large cell populations, one cell at a time. The resulting epigenomic information provides unprecedented insight into the different cell types that come together to form organs and organ systems, as well as pathogenic modifications associated with disease.

Every single cell has unique epigenomic instructions that guide how it expresses its genes and these instructions are subject to change. A map locating epigenetic modifications in the genome would help scientists understand how epigenetics drives cellular differentiation. But until recently, epigenetic assays mainly focused on select regions of DNA or gave bulk results across an entire sample of cells.[ii] These assays were not designed to detect epigenetic patterns in individual cells.

Single-cell tools like scATAC-seq help us get a grasp on intracellular heterogeneity, differentiate between cell populations and map the role of epigenetics in the larger context of an organism. By building a collection of scATAC-seq data, scientists have begun generating a cell atlas to provide insight into the role of epigenetics during the intricate biological processes that occur throughout the human lifetime.

During ATAC-seq, a hyperactive transposase mutant, Tn5, binds to open chromatin (euchromatin) regions. Wherever Tn5 binds, it cleaves the DNA and attaches sequencing adapters. Then, after PCR amplification, ATAC fragments are sequenced to identify open chromatin regions. ATAC results indicate where nucleosomes are typically positioned in the cell sample and which regions of the genome are open for transcription factors to bind. As such, scientists use ATAC-Seq as a first-pass screening approach to identify changes in chromatin accessibility between samples.

ATAC-seq has many practical applications, but it cant account for the cell-to-cell variability thats often an important aspect of developmental processes and disease. So, researchers developed a new assay in which microfluidic technology is used to isolate individual cells before ATAC-seq.[iv] This assay provides epigenomic information at single cell resolution, earning it the name scATAC-seq.

The key to the scATAC-seq method is that it isolates genomes of individual cells early on to perform a separate ATAC-seq reaction on each individual cell. Then, open regions of the genome are cleaved by the Tn5 transposase, tagged with sequencing adapters and amplified with barcoded cell-identifying primers. Subsequently, the barcoded libraries of ATAC fragments, (each representing an individual cell) are pooled together and sequenced to reveal open chromatin regions of thousands of individual cells.

The first droplet-based iteration of the scATAC-seq method (dscATAC-seq) uses a single cell isolator to encapsulate thousands of individual nuclei in nanoliter-sized droplets for ATAC sequencing. It uses a custom Tn5 transposase to enhance library complexity and signal resolution. Compared to the original microfluidic method, the new workflow is faster and yields greater biological insight with less time and effort spent on sequencing. To demonstrate its power and potential, this technique has been used to conduct an unbiased analysis of the many different cell types and regulatory elements in a mouse brain. [v]

Figure 1:In scATAC-seq, droplet-based technology partitions thousands of whole cells or nuclei into individual nanoliter-sized droplets, enabling researchers to prepare a library of ATAC fragments for sequencing to reveal open chromatin regions. Credit:Bio-Rad Laboratories.

To capture single cell data on a truly massive scale, combinatorial indexing was next introduced into the dscATAC-seq workflow. This new method, called dsciATAC-seq, enables researchers to assess up to 50,000 cells in a single assay. Assaying a large volume of cells is possible because, in dsciATAC-seq, the hyperactive mutant transposase integrates a first set of barcodes as it cleaves open regions of chromatin in each nucleus. Because every cells DNA already carries a barcode, multiple cells can be loaded into a single droplet. Then, as usual, ATAC fragments are amplified with a second set of barcoded primers. After sequencing these fragments, the two sets of barcodes are used to derive epigenomic profiles for tens of thousands of cells.

Putting the dsciATAC-seq method to the test, researchers have studied immune cell clusters from human bone marrow derived cells to illustrate how the chromatin accessibility landscape in these cells changes according to different stimulants at the single cell level.5Although the number of cells that a single scATAC-seq experiment can evaluate has grown dramatically, it will take a continued concerted effort from scientists across many disciplines to create a comprehensive map of the human epigenome, encompassing data from trillions of cells.[vi] Furthermore, to help decode the patterns we find in the human epigenome, it may be valuable to gather information about the epigenomes of animals commonly used as research models. As each of these maps become increasingly detailed, scientists will gain a more thorough understanding of how biological process work and may apply this knowledge towards developing better treatments for complex diseases.

Reference:

[i] Egger, G., et al. Epigenetics in human disease and prospects for epigenetic therapy. Nature, 2004, 429, 457463. doi:10.1038/nature02625[ii] DeAngelis, J. T., Farrington, W. J., & Tollefsbol, T. O. An overview of epigenetic assays. Molecular biotechnology, 2008, 38(2), 179183. doi:10.1007/s12033-007-9010-y[iii] Buenrostro JD, Giresi PG, Zaba LC, Chang HY, Greenleaf WJ. Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position. Nature Methods, 2013, 10(12):1213-8. doi: 10.1038/nmeth.2688.[iv] Buenrostro JD, Wu B, Litzenburger UM, Ruff D, Gonzales ML, Snyder MP, Chang HY, Greenleaf WJ. Single-cell chromatin accessibility reveals principles of regulatory variation. Nature, 2015, 523(7561):486-90. doi: 10.1038/nature14590.[v] Lareau, C.A., Duarte, F.M., Chew, J.G. et al. Droplet-based combinatorial indexing for massive-scale single-cell chromatin accessibility. Nature Biotechnology 37, 916924 (2019) doi:10.1038/s41587-019-0147-6.[vi] Bianconi, E., Piovesan, A., Facchin F., Beraudi, A., Casadei. R., Frabetti, F., Vitale, L., Pelleri, M., Tassani. S., Piva, F., Perez-Amodio, S, Strippoli, P. & Canaider, S. An estimation of the number of cells in the human body. Annals of Human Biology, 2013, 40:6, 463-471. doi: 10.3109/03014460.2013.807878.

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Using Single Cells To Get the Whole Picture of the Epigenome - Technology Networks

Bone Marrow Stem Cells Comments Off on Using Single Cells To Get the Whole Picture of the Epigenome – Technology Networks | March 13th, 2020

Global Stem Cell Therapy Market: Overview

Also called regenerative medicine, stem cell therapy encourages the reparative response of damaged, diseased, or dysfunctional tissue via the use of stem cells and their derivatives. Replacing the practice of organ transplantations, stem cell therapies have eliminated the dependence on availability of donors. Bone marrow transplant is perhaps the most commonly employed stem cell therapy.

Osteoarthritis, cerebral palsy, heart failure, multiple sclerosis and even hearing loss could be treated using stem cell therapies. Doctors have successfully performed stem cell transplants that significantly aid patients fight cancers such as leukemia and other blood-related diseases.

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Global Stem Cell Therapy Market: Key Trends

The key factors influencing the growth of the global stem cell therapy market are increasing funds in the development of new stem lines, the advent of advanced genomic procedures used in stem cell analysis, and greater emphasis on human embryonic stem cells. As the traditional organ transplantations are associated with limitations such as infection, rejection, and immunosuppression along with high reliance on organ donors, the demand for stem cell therapy is likely to soar. The growing deployment of stem cells in the treatment of wounds and damaged skin, scarring, and grafts is another prominent catalyst of the market.

On the contrary, inadequate infrastructural facilities coupled with ethical issues related to embryonic stem cells might impede the growth of the market. However, the ongoing research for the manipulation of stem cells from cord blood cells, bone marrow, and skin for the treatment of ailments including cardiovascular and diabetes will open up new doors for the advancement of the market.

Global Stem Cell Therapy Market: Market Potential

A number of new studies, research projects, and development of novel therapies have come forth in the global market for stem cell therapy. Several of these treatments are in the pipeline, while many others have received approvals by regulatory bodies.

In March 2017, Belgian biotech company TiGenix announced that its cardiac stem cell therapy, AlloCSC-01 has successfully reached its phase I/II with positive results. Subsequently, it has been approved by the U.S. FDA. If this therapy is well- received by the market, nearly 1.9 million AMI patients could be treated through this stem cell therapy.

Another significant development is the granting of a patent to Israel-based Kadimastem Ltd. for its novel stem-cell based technology to be used in the treatment of multiple sclerosis (MS) and other similar conditions of the nervous system. The companys technology used for producing supporting cells in the central nervous system, taken from human stem cells such as myelin-producing cells is also covered in the patent.

The regional analysis covers:

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Global Stem Cell Therapy Market: Regional Outlook

The global market for stem cell therapy can be segmented into Asia Pacific, North America, Latin America, Europe, and the Middle East and Africa. North America emerged as the leading regional market, triggered by the rising incidence of chronic health conditions and government support. Europe also displays significant growth potential, as the benefits of this therapy are increasingly acknowledged.

Asia Pacific is slated for maximum growth, thanks to the massive patient pool, bulk of investments in stem cell therapy projects, and the increasing recognition of growth opportunities in countries such as China, Japan, and India by the leading market players.

Global Stem Cell Therapy Market: Competitive Analysis

Several firms are adopting strategies such as mergers and acquisitions, collaborations, and partnerships, apart from product development with a view to attain a strong foothold in the global market for stem cell therapy.

Some of the major companies operating in the global market for stem cell therapy are RTI Surgical, Inc., MEDIPOST Co., Ltd., Osiris Therapeutics, Inc., NuVasive, Inc., Pharmicell Co., Ltd., Anterogen Co., Ltd., JCR Pharmaceuticals Co., Ltd., and Holostem Terapie Avanzate S.r.l.

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Stem Cell Therapy Market Report on Recent Adoption 2025 - 3rd Watch News

Bone Marrow Stem Cells Comments Off on Stem Cell Therapy Market Report on Recent Adoption 2025 – 3rd Watch News | March 13th, 2020

A second patient has been cured of HIV after undergoing stem cell transplant treatment, doctors said Tuesday, after finding no trace of infection 30 months after he stopped traditional treatment.

The so-called "London Patient", a cancer sufferer originally from Venezuela, made headlines last year when researchers at the University of Cambridge reported they had found no trace of the AIDS-causing virus in his blood for 18 months.

Ravindra Gupta, lead author of the study published in The Lancet HIV, said the new test results were "even more remarkable" and likely demonstrated the patient was cured.

"We've tested a sizeable set of sites that HIV likes to hide in and they are all pretty much negative for an active virus," Gupta told AFP.

The patient, who revealed his identity this week as Adam Castillejo, 40, was diagnosed with HIV in 2003 and had been on medication to keep the disease in check since 2012.

Later that year, he was diagnosed with advanced Hodgkin's Lymphoma, a deadly cancer.

In 2016 he underwent a bone marrow transplant to treat blood cancer, receiving stem cells from donors with a genetic mutation present in less than one percent of Europeans that prevents HIV from taking hold.

He becomes only the second person to be cured of HIV after American Timothy Brown, known as the "Berlin Patient", recovered from HIV in 2011 following similar treatment.

Viral tests of Castillejo's cerebral fluid, intestinal tissue and lymphoid tissue more than two years after stopping antiretroviral treatment showed no active infection.

Gupta said the tests uncovered HIV "fossils" - fragments of the virus that were now incapable of reproducing, and were therefore safe.

"We'd expect that," he said.

"It's quite hard to imagine that all trace of a virus that infects billions of cells was eliminated from the body."

Researchers cautioned that the breakthrough did not constitute a generalised cure for HIV, which leads to nearly one million deaths every year.

Castillejo's treatment was a "last resort" as his blood cancer would likely have killed him without intervention, according to Gupta.

The Cambridge doctor said that there were "several other" patients who had undergone similar treatment but who were less far along in their remission.

"There will probably be more but they will take time," he said.

Researchers are currently weighing up whether or not patients suffering from drug-resistant forms of HIV might be eligible for stem cell transplants in future, something Gupta said would require careful ethical consideration.

"You'd have to weigh up the fact that there's a 10-percent mortality rate from doing a stem-cell transplant against what the risk of death would be if we did nothing," he said.

Castillejo himself said that the experience had prompted him to come forward and identify himself in order to help spread awareness of HIV.

This is a unique position to be in, a unique and very humbling position," he told The New York Times.

Sharon Lewin, an infectious disease expert at the University of Melbourne and member of the International AIDS Society, said Castillejo's case was "exciting".

"But we need to also place it in context - curing people of HIV via a bone marrow transplant is just not a viable option on any kind of scale," she said.

"We need to constantly reiterate the importance of, prevention, early testing and treatment adherence as the pillars of the current global response to HIV/AIDS."

Agence France-Presse

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Second Person Declared 'Cured' of HIV, With No Trace of Infection After Nearly 3 Years - ScienceAlert

Bone Marrow Stem Cells Comments Off on Second Person Declared ‘Cured’ of HIV, With No Trace of Infection After Nearly 3 Years – ScienceAlert | March 12th, 2020

In early September 2017, my daughters came home from daycare with a stomach bug that made its way around the house. Everyone else got over it pretty quickly, but I didnt. Instead, I became the sickest Ive ever been in my life with a high fever, relentless cough, chills, and vomiting to the point where I couldnt even keep down a few sips of water.

Before this, Id been in relatively good health. At 32, Id just returned to work as an attorney in the Dallas, Texas, area after maternity leave (I'm a mom of three) and I never took sick days. But for three days, I stayed home.

All I could really do was lay in bed under the blankets, hoping whatever illness I had would pass. After several days of not being able to keep any food or water down, I finally went to urgent care. There, a doctor ran blood work, gave me Zofran (an anti-nausea med), and sent me home.

Two days later, I received a call from the urgent care office.

They wouldnt tell me anything specific about my blood work but they advised me to schedule an appointment with my primary care doctor. As I didnt have one, I scheduled an appointment with a new doctor who wouldnt be able to see me for several weeks.

As the days went on, I still couldnt keep any food down and I started researching my symptoms to try to figure out what was wrong with me. I thought maybe I had a vitamin B12 deficiency and headed into urgent care again. There, the doctor advised me to go straight to the emergency room at the hospital down the street for fluids, a blood transfusion, and an appointment with a hematologist. At the ER, I did just that and was discharged with an appointment scheduled for two days later.

The next morning, a nurse from the hematologists office called and asked if I could come in that day. She told me there was a chance that the doctor might hospitalize me, so I might want to pack a bag.

I held out hope that it wasnt a big deal, but I should have realized I was seriously ill.

I was too weak to drive, so my husband took me to my appointment. There, the hematologist told me that they needed to confirm my exact diagnosis with further testing, but based on my blood panels, I had a form of blood cancer, also known as leukemia.

Although Google had told me that this was a possibility when Id begun researching my symptoms, it had seemed so imaginable. It felt surreal. People were talking around me and about me, but I dont remember much of what they were saying. I was wheeled directly to the hospital across the street and immediately admitted. The first step was to get me into a stable condition.

Leukemia causes your body to produce an abundance of white blood cells, many of which are abnormal. And the white blood cells crowd out your red blood cells and platelets, which deprives your body of oxygen and prevents blood clotting. Because I was dehydrated and dangerously anemic, I received fluids and several units of blood. Afterwards, I felt better than I had in weeks.

The doctor ran a whole host of tests to determine which type of blood cancer I had, how widespread it was, and if I had any chromosomal mutations, as those would inform the proper treatment for me.

About a week later, I was given an official diagnosis of acute myeloid leukemia.

It's also called (AML), and it's a rapidly progressive cancer of the blood and bone marrow that affects white blood cells known as myeloid cells. Within the United States, there are over 20,000 new cases every year, but the majority of those affected are older adults. When I asked how I ended up with this condition, my hematologist explained that my case wasnt genetic but probably just random bad luck.

In most cases of AML, its not clear what exactly causes the DNA damage that in turn leads to the haywire production of abnormal white blood cells. Many people who end up with this type of blood cancer, like me, have no known risk factors (some of which include being a smoker, male, and over the age of 65). Early signs of AML, including fever, body aches, and fatigue, often seem like a case of the flu or bug.

In October 2017, a month after my stomach bug first appeared, I was readmitted to the hospital and began a round of intensive remission induction chemotherapy in order to kill the leukemia cells in my blood and bone marrow.

For my first round, I stayed in the hospital for about a month. I was not allowed to leave the clean floor, where filtered air was continuously pumped into the rooms and visitors were scanned for fever and illness before they were able to be near any patients. Staff and visitors wore face masks and plastic smocks as an additional layer of protection.

The hardest part of chemo was that my daughters were not allowed on my hospital floor.

Children under 12 weren't allowed on the "clean floor," so I wasnt able to see my daughters for almost a month. We used FaceTime a few times, which was simultaneously great and excruciating because I just wanted to reach out and snuggle them but I knew I couldnt.

Every morning, my medical team would check my blood cell counts to determine if Id need a unit of blood or platelet infusion. I couldnt be discharged from the hospital until my white blood cell count had recovered enough from the chemotherapy for it to be safe for me to leave the clean floor.

After the induction round, I was discharged. Another bone marrow biopsy showed that I was in complete remission, meaning that my blast count in my bone marrow was less than 5 percent. But I wasnt totally in the clear just yet.

For my second half of treatment, I had to undergo four more rounds of consolidation chemotherapy to destroy any remaining cancer cells in order to lower my risk of relapse. While these rounds were gentler, I still struggled. Eight weeks in, my bone marrow was so severely damaged from chemotherapy it began to fail, and I had to get a transplant.

The transplant itself only took about an hour. But after that, it was a waiting game. Every day, my blood was tested, and we waited for the new stem cells to start producing new blood cells and immune system cells. I was also monitored carefully for any signs of infection, which is a huge risk after this type of procedure. My blood cell counts steadily rose, and I was discharged from the hospital after 28 days.

By August 2018, nearly a year into my journey, I went back to work and resumed my normal life.

A few months later, in October, I participated in Light the Night, a celebratory walk and fundraiser sponsored by the Leukemia & Lymphoma Society (LLS). At the event, I heard about another LLS fundraiser, The Big Climb Dallas, where participants climb the tallest building in the city: the Bank of America Tower. Its 70 flights of stairs. and I had no idea if I could do that, but Id caught the fundraising bug. I recruited about 30 friends, family members, and coworkers to climb with me, and I made it to the top.

As the leader of one of the top fundraising teams, I was asked to join the planning committee for the Big Climb 2020, which I enthusiastically accepted. This year, I was extremely grateful to be named the Honored Hero of Big Climb Dallas 2020 and to represent survivors and supporters whose lives have been touched by blood cancer.

It was a long process to get diagnosed and treated, but two and a half years later, Im in full remission.

Funny enough, Im ultimately thankful that my daughters got sick at daycare (as strange as that might sound). If they hadnt, I may have gone several more months before getting a diagnosis and treatment. Today, Im happy to share my story in the hopes that it might help even one other person.

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My Flu Symptoms Turned Out To Be Acute Myeloid Leukemia - Women's Health

Bone Marrow Stem Cells Comments Off on My Flu Symptoms Turned Out To Be Acute Myeloid Leukemia – Women’s Health | March 12th, 2020

VANCOUVER, Washington, March 12, 2020 (GLOBE NEWSWIRE) -- CytoDyn Inc. (OTC.QB: CYDY), (CytoDyn or the Company), a late-stage biotechnology company developing leronlimab (PRO 140), a CCR5 antagonist with the potential for multiple therapeutic indications, announced today that the FDA recommended that the Company request a preliminary Breakthrough Therapy designation meeting. Meanwhile, the Company continues reporting very positive data for its mTNBC and MBC patients.

Metastatic triple-negative breast cancer (mTNBC), an aggressive histological subtype, has a poor prognosis. In addition, metastatic breast cancer (MBC) is breast cancer that has spread beyond the breast and lymph nodes to other organs in the body (typically the bones, liver, lungs, or brain). Both types of cancer pose significant challenges for patients due to their aggressiveness and limited treatment options. An integral part of CytoDyns mission and purpose is to provide effective therapeutic solutions to these patients. Clinical results from the first cancer patient in the Companys Phase 1b/2 mTNBC trial are as follows:

Patient #1: Enrolled in mTNBC Phase 1b/2 with first treatment in late September 2019. CTC (circulating tumor cells) dropped to zero after two treatments with leronlimab and carboplatin. Total CTC and EMT (Epithelial Mesenchymal Transition in Tumor Metastasis) dropped to zero after about one month of treatment with leronlimab (once-a-week 350 mg dose). Results from the patients earlier CT scan indicated a more than 25% tumor shrinkage within the first few weeks of treatment with leronlimab and carboplatin. After approximately five months of treatment with leronlimab and carboplatin, the patient not only has zero CTC and zero EMT, but also zero detectible CAML (cancer-associated microphages like cells). The patients oncologist has now ordered this patients treatment to consist only of leronlimab and has discontinued treatment with carboplatin (a chemotherapy drug). Testimony provided to the Company from the patient stated: So far my experience with leronlimab has been very positive. I didnt expect it to be so easy and tolerable with virtually ZERO side effects. The results so far have been super impressive. Im very grateful to be part of this clinical trial study and it really makes me feel hopeful that this otherwise fatal disease can be turned into a manageable disease in the near future.

Bruce Patterson, M.D., chief executive officer and founder of IncellDx, a diagnostic partner and advisor to CytoDyn, commented, The FDA recommendation for a meeting on CytoDyns BTD application is a tremendous opportunity to further discuss the mechanism of action and to summarize the promising results from patients enrolled following the submission of the application. Included in this discussion will be the recent decision by the oncologist of Patient #1 to, based on continued unremarkable changes to her condition, remove carboplatin from the patients regimen with continued therapy with leronlimab. Nader Pourhassan, Ph.D., president and chief executive officer of CytoDyn, added: Our first patient in the Phase 1b/2 trial has shown remission of the tumor and her oncologist has attributed this primarily to leronlimab and discontinued the carboplatin (a form of chemotherapy). This patients latest results of zero CTC, EMT, and CAML is unique and we now have another patient with three zeros identical to the first patient. We are very excited to continue enrolling patients and hopeful to have our first patient treated in our basket trial for 22 solid tumor cancers very soon. We are also very hopeful to have several more patients in our Phase 1b/2 mTNBC trial before our preliminary meeting with the FDA for Breakthrough Therapy designation.

About Triple-Negative Breast CancerTriple-negative breast cancer (TNBC) is a type of breast cancer characterized by the absence of the three most common types of receptors in the cancer tumor known to fuel most breast cancer growthestrogen receptors (ER), progesterone receptors (PR) and the hormone epidermal growth factor receptor 2 (HER-2) gene. TNBC cancer occurs in about 10 to 20 percent of diagnosed breast cancers and can be more aggressive and more likely to spread and recur. Since the triple-negative tumor cells lack these receptors, common treatments for breast cancer such as hormone therapy and drugs that target estrogen, progesterone, and HER-2 are ineffective.

About Leronlimab (PRO 140) The U.S. Food and Drug Administration (FDA) have granted a Fast Track designation to CytoDyn for two potential indications of leronlimab for deadly diseases. The first as a combination therapy with HAART for HIV-infected patients and the second is for metastatic triple-negative breast cancer. Leronlimab is an investigational humanized IgG4 mAb that blocks CCR5, a cellular receptor that is important in HIV infection, tumor metastases, and other diseases including NASH. Leronlimab has successfully completed nine clinical trials in over 800 people, including meeting its primary endpoints in a pivotal Phase 3 trial (leronlimab in combination with standard antiretroviral therapies in HIV-infected treatment-experienced patients).

In the setting of HIV/AIDS, leronlimab is a viral-entry inhibitor; it masks CCR5, thus protecting healthy T cells from viral infection by blocking the predominant HIV (R5) subtype from entering those cells. Leronlimab has been the subject of nine clinical trials, each of which demonstrated that leronlimab can significantly reduce or control HIV viral load in humans. The leronlimab antibody appears to be a powerful antiviral agent leading to potentially fewer side effects and less frequent dosing requirements compared with daily drug therapies currently in use.

In the setting of cancer, research has shown that CCR5 plays an important role in tumor invasion and metastasis. Increased CCR5 expression is an indicator of disease status in several cancers. Published studies have shown that blocking CCR5 can reduce tumor metastases in laboratory and animal models of aggressive breast and prostate cancer. Leronlimab reduced human breast cancer metastasis by more than 98% in a murine xenograft model. CytoDyn is therefore conducting a Phase 1b/2 human clinical trial in metastatic triple-negative breast cancer and was granted Fast Track designation in May 2019. Additional research is being conducted with leronlimab in the setting of cancer and NASH with plans to conduct additional clinical studies when appropriate.

The CCR5 receptor appears to play a central role in modulating immune cell trafficking to sites of inflammation and may be important in the development of acute graft-versus-host disease (GvHD) and other inflammatory conditions. Clinical studies by others further support the concept that blocking CCR5 using a chemical inhibitor can reduce the clinical impact of acute GvHD without significantly affecting the engraftment of transplanted bone marrow stem cells. CytoDyn is currently conducting a Phase 2 clinical study with leronlimab to further support the concept that the CCR5 receptor on engrafted cells is critical for the development of acute GvHD and that blocking this receptor from recognizing certain immune signaling molecules is a viable approach to mitigating acute GvHD. The FDA has granted orphan drug designation to leronlimab for the prevention of GvHD.

About CytoDyn CytoDyn is a biotechnology company developing innovative treatments for multiple therapeutic indications based on leronlimab, a novel humanized monoclonal antibody targeting the CCR5 receptor. CCR5 appears to play a key role in the ability of HIV to enter and infect healthy T-cells. The CCR5 receptor also appears to be implicated in tumor metastasis and in immune-mediated illnesses, such as GvHD and NASH. CytoDyn has successfully completed a Phase 3 pivotal trial with leronlimab in combination with standard anti-retroviral therapies in HIV-infected treatment-experienced patients. CytoDyn plans to seek FDA approval for leronlimab in combination therapy and plans to complete the filing of a Biologics License Application (BLA) in the first quarter of 2020 for that indication. CytoDyn is also conducting a Phase 3 investigative trial with leronlimab as a once-weekly monotherapy for HIV-infected patients and plans to initiate a registration-directed study of leronlimab monotherapy indication, which if successful, could support a label extension. Clinical results to date from multiple trials have shown that leronlimab can significantly reduce viral burden in people infected with HIV with no reported drug-related serious adverse events (SAEs). Moreover, results from a Phase 2b clinical trial demonstrated that leronlimab monotherapy can prevent viral escape in HIV-infected patients, with some patients on leronlimab monotherapy remaining virally suppressed for more than five years. CytoDyn is also conducting a Phase 2 trial to evaluate leronlimab for the prevention of GvHD and a Phase 1b/2 clinical trial with leronlimab in metastatic triple-negative breast cancer. More information is at http://www.cytodyn.com.

Forward-Looking Statements This press release contains certain forward-looking statements that involve risks, uncertainties and assumptions that are difficult to predict. Words and expressions reflecting optimism, satisfaction or disappointment with current prospects, as well as words such as believes, hopes, intends, estimates, expects, projects, plans, anticipates and variations thereof, or the use of future tense, identify forward-looking statements, but their absence does not mean that a statement is not forward-looking. The Companys forward-looking statements are not guarantees of performance, and actual results could vary materially from those contained in or expressed by such statements due to risks and uncertainties including: (i) the sufficiency of the Companys cash position, (ii) the Companys ability to raise additional capital to fund its operations, (iii) the Companys ability to meet its debt obligations, if any, (iv) the Companys ability to enter into partnership or licensing arrangements with third parties, (v) the Companys ability to identify patients to enroll in its clinical trials in a timely fashion, (vi) the Companys ability to achieve approval of a marketable product, (vii) the design, implementation and conduct of the Companys clinical trials, (viii) the results of the Companys clinical trials, including the possibility of unfavorable clinical trial results, (ix) the market for, and marketability of, any product that is approved, (x) the existence or development of vaccines, drugs, or other treatments that are viewed by medical professionals or patients as superior to the Companys products, (xi) regulatory initiatives, compliance with governmental regulations and the regulatory approval process, (xii) general economic and business conditions, (xiii) changes in foreign, political, and social conditions, and (xiv) various other matters, many of which are beyond the Companys control. The Company urges investors to consider specifically the various risk factors identified in its most recent Form 10-K, and any risk factors or cautionary statements included in any subsequent Form 10-Q or Form 8-K, filed with the Securities and Exchange Commission. Except as required by law, the Company does not undertake any responsibility to update any forward-looking statements to take into account events or circumstances that occur after the date of this press release.

CYTODYN CONTACTS

Investors: Dave Gentry, CEO RedChip Companies Office: 1.800.RED.CHIP (733.2447) Cell: 407.491.4498 dave@redchip.com

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CytoDyn's First mTNBC Patient in Phase 1b/2 is in Remission and Oncologist Ordered Termination of Treatment with Carboplatin (chemotherapy drug) and...

Bone Marrow Stem Cells Comments Off on CytoDyn’s First mTNBC Patient in Phase 1b/2 is in Remission and Oncologist Ordered Termination of Treatment with Carboplatin (chemotherapy drug) and… | March 12th, 2020

MENLO PARK, Calif. and NEW YORK, March 11, 2020 (GLOBE NEWSWIRE) -- Forty Seven Inc. (Nasdaq: FTSV) and Rocket Pharmaceuticals Inc. (Nasdaq: RCKT) announced today that they have entered into a research collaboration to pursue clinical proof-of-concept for Forty Sevens novel antibody-based conditioning regimen, FSI-174 (anti-cKIT antibody) plus magrolimab (anti-CD47 antibody), with Rockets ex vivo lentiviral vector hematopoietic stem cell (LVV HSC) gene therapy, RP-L102. The initial collaboration will evaluate this treatment regimen in Fanconi Anemia (FA), a genetic disease that affects patients capacity to produce blood cells and is associated with an increased risk of leukemia and other neoplasms. RP-L102, Rockets gene therapy approach for FA, involves treatment with patients own gene-corrected blood forming stem cells (hematopoietic stem cells, or HSCs).

Gene therapies for monogenic blood disorders have broad potential. One concern associated with these treatments is the toxicity of pre-therapy conditioning regimens that utilize cytotoxic chemotherapy and/or radiation to destroy existing HSCs and facilitate engraftment of gene-corrected HSCs. Forty Sevens all-antibody based conditioning regimen is designed to address the limitations of current pre-treatment conditioning therapies. These regimens are often associated with serious side effects, including severe infection, cognitive impairment, infertility, endocrine dysfunction, secondary malignancies and organ damage. These toxicities are especially difficult for pediatric patients and are particularly severe for patients with FA, who are more sensitive to the DNA-damaging effects of traditional conditioning agents. Preliminary data demonstrate that RP-L102 may confer efficacy without pre-treatment conditioning. The combination of RP-L102 with Forty Sevens all-antibody conditioning regimen may provide patients an alternate treatment option in situations where conditioning may be advantageous.

We are pleased to enter into this collaboration with Forty Seven, said Jonathan Schwartz, M.D., Chief Medical Officer and Senior Vice President of Rocket. RP-L102 Process B is currently being evaluated in a registrational trial without the use of conditioning. In parallel, we are assessing incorporation of a non-genotoxic conditioning regimen as a part of Rockets life-cycle management strategy. Forty Sevens novelall-antibodyconditioning regimen could also beapplied to Rockets other lentiviral programs, in which conditioning is more integral to the gene therapy approach.

We are initiating our first in human healthy volunteer study of FSI-174 in the first quarter this year, and are excited to enter into a partnership with Rocket at this time. Rocket is at the forefront of developing gene therapies for high unmet-need diseases, and this collaboration will provide an opportunity to evaluate the benefit of Forty Sevens novel conditioning regimen with Rockets RP-L102 to help FA patients, says Jens-Peter Volkmer, VP of Research at Forty Seven.

This collaboration is in line with our strategy to study our anti-cKIT and anti-CD47, all-antibody conditioning regimen in combination with several different gene therapies, and to establish clinical proof-of-concept in a broad range of transplant indications, said Mukul Agarwal, VP of Corporate Development at Forty Seven.

Maria Grazia Roncarolo, M.D., Scientific Advisor to Forty Seven, commented, The goal of my lifes work is to bring pediatric patients transformative therapies for currently incurable diseases. We believe Rocket Pharmaceuticals commitment to devastating diseases, such as FA, addresses a critical unmet need and Forty Sevens antibody conditioning creates an alternative avenue to deliver this therapy to those patients. We look forward to seeing how this collaboration may help patients in need.

Under the terms of the agreement, Rocket will provide its ex vivo LVV HSC gene therapy platform and Forty Seven will contribute its innovative antibody-based conditioning regimen for the collaboration.

About FSI-174 and MagrolimabFSI-174 is a humanized monoclonal antibody targeting cKIT, which is a receptor that is highly expressed on hematopoietic stem cells. Magrolimab is a humanized monoclonal antibody targeting CD47, which is a dont eat me signal to macrophages and is expressed on all cells. Magrolimab is currently being investigated in Phase 2 clinical trials to treat cancer and has established clinical efficacy in four indications, including myelodysplastic syndrome, acute myeloid leukemia, diffuse large B cell lymphoma and follicular lymphoma, with a favorable safety profile in over 400 patients treated, including some patients treated continuously for over two years. When combined, FSI-174 sends a positive signal to macrophages to target blood forming stem cells for removal and magrolimab disengages inhibitory signals that block phagocytosis. Combination of these antibodies has shown efficient removal of blood forming stem cells, allowing for transplantation in pre-clinical models.

About Fanconi Anemia Fanconi Anemia (FA) is a rare pediatric disease characterized by bone marrow failure, malformations and cancer predisposition. The primary cause of death among patients with FA is bone marrow failure, which typically occurs during the first decade of life. Allogeneic hematopoietic stem cell transplantation (HSCT), when available, corrects the hematologic component of FA, but requires myeloablative conditioning. Graft-versus-host disease, a known complication of allogeneic HSCT, is associated with an increased risk of solid tumors, mainly squamous cell carcinomas of the head and neck region. Approximately 60-70% of patients with FA have aFANC-Agene mutation, which encodes for a protein essential for DNA repair. Mutation in theFANC-Agene leads to chromosomal breakage and increased sensitivity to oxidative and environmental stress. Chromosome fragility induced by DNA-alkylating agents such as mitomycin-C (MMC) or diepoxybutane (DEB) is the gold standard test for FA diagnosis. Somatic mosaicism occurs when there is a spontaneous correction of the mutated gene that can lead to stabilization or correction of a FA patients blood counts in the absence of any administered therapy. Somatic mosaicism, often referred to as natural gene therapy provides a strong rationale for the development of FA gene therapy because of the selective growth advantage of gene-corrected hematopoietic stem cells over FA cells1.

1Soulier, J.,et al. (2005) Detection of somatic mosaicism and classification of Fanconi anemia patients by analysis of the FA/BRCA pathway. Blood 105: 1329-1336

About Rocket Pharmaceuticals, Inc. Rocket Pharmaceuticals, Inc. (Nasdaq: RCKT) (Rocket) is advancing an integrated and sustainable pipeline of genetic therapies that correct the root cause of complex and rare childhood disorders. The companys platform-agnostic approach enables it to design the best therapy for each indication, creating potentially transformative options for patients contending with rare genetic diseases. Rocket's clinical programs using lentiviral vector (LVV)-based gene therapy are for the treatment of Fanconi Anemia (FA), a difficult to treat genetic disease that leads to bone marrow failure and potentially cancer, Leukocyte Adhesion Deficiency-I (LAD-I), a severe pediatric genetic disorder that causes recurrent and life-threatening infections which are frequently fatal, and Pyruvate Kinase Deficiency (PKD) a rare, monogenic red blood cell disorder resulting in increased red cell destruction and mild to life-threatening anemia. Rockets first clinical program using adeno-associated virus (AAV)-based gene therapy is for Danon disease, a devastating, pediatric heart failure condition. Rockets pre-clinical pipeline program is for Infantile Malignant Osteopetrosis (IMO), a bone marrow-derived disorder. For more information about Rocket, please visitwww.rocketpharma.com.

For more information, please visit http://www.rocketpharma.com or contact info@rocketpharma.com

About Forty Seven, Inc.Forty Seven, Inc.is a clinical-stage immuno-oncology company that is developing therapies targeting cancer immune evasion pathways based on technology licensed fromStanford University. Forty Sevens lead program, magrolimab, is a monoclonal antibody against the CD47 receptor, a dont eat me signal that cancer cells commandeer to avoid being ingested by macrophages. This antibody is currently being evaluated in multiple clinical studies in patients with myelodysplastic syndrome, acute myeloid leukemia, and non-Hodgkins lymphoma.

For more information, please visitwww.fortyseveninc.comor contactinfo@fortyseveninc.com.

Follow Forty Seven on social media:@FortySevenInc,LinkedIn

Rocket Cautionary Statement Regarding Forward-Looking StatementsVarious statements in this release concerning Rocket's future expectations, plans and prospects, including without limitation, Rocket's expectations regarding the safety, effectiveness and timing of product candidates that Rocket may develop, to treat Fanconi Anemia (FA), Leukocyte Adhesion Deficiency-I (LAD-I), Pyruvate Kinase Deficiency (PKD), Infantile Malignant Osteopetrosis (IMO) and Danon Disease, and the safety, effectiveness and timing of related pre-clinical studies and clinical trials, may constitute forward-looking statements for the purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995 and other federal securities laws and are subject to substantial risks, uncertainties and assumptions. You should not place reliance on these forward-looking statements, which often include words such as "believe," "expect," "anticipate," "intend," "plan," "will give," "estimate," "seek," "will," "may," "suggest" or similar terms, variations of such terms or the negative of those terms. Although Rocket believes that the expectations reflected in the forward-looking statements are reasonable, Rocket cannot guarantee such outcomes. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including, without limitation, Rocket's ability to successfully demonstrate the efficacy and safety of such products and pre-clinical studies and clinical trials, its gene therapy programs, the preclinical and clinical results for its product candidates, which may not support further development and marketing approval, the potential advantages of Rocket's product candidates, actions of regulatory agencies, which may affect the initiation, timing and progress of pre-clinical studies and clinical trials of its product candidates, Rocket's and its licensors ability to obtain, maintain and protect its and their respective intellectual property, the timing, cost or other aspects of a potential commercial launch of Rocket's product candidates, Rocket's ability to manage operating expenses, Rocket's ability to obtain additional funding to support its business activities and establish and maintain strategic business alliances and new business initiatives, Rocket's dependence on third parties for development, manufacture, marketing, sales and distribution of product candidates, the outcome of litigation, and unexpected expenditures, as well as those risks more fully discussed in the section entitled "Risk Factors" in Rocket's Annual Report on Form 10-K for the year ended December 31, 2019, filed March 6, 2020 with the SEC. Accordingly, you should not place undue reliance on these forward-looking statements. All such statements speak only as of the date made, and Rocket undertakes no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise.

Forty Seven Cautionary Statement Regarding Forward-Looking StatementsStatements contained in this press release regarding matters that are not historical facts are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as will, may, assess, could, believe, and similar expressions (as well as other words or expressions referencing future events, conditions, or circumstances) are intended to identify forward-looking statements. These statements include those related to the research and development plans for Rockets and Forty Sevens respective platforms and product candidates, the timing and success of Forty Sevens collaboration with Rocket, Forty Sevens plans to pursue clinical proof-of-concept for FSI-174 plus magrolimab with the LVV HSC gene therapy platform, the focus on diseases that have the potential to be corrected with the combination of RP-L102 and Forty Sevens all-antibody conditioning regimen, the tolerability and efficacy of RP-L102, FSI-174 and magrolimab, the timing and success of any future collaborations between Forty Seven and Rocket, Forty Sevens plans to continue development of FSI-174 plus magrolimab, as well as related timing for clinical trials of the same.

Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. The product candidates that Forty Seven develops may not progress through clinical development or receive required regulatory approvals within expected timelines or at all.In addition, clinical trials may not confirm any safety, potency or other product characteristics described or assumed in this press release. Such product candidates may not be beneficial to patients or successfully commercialized. The failure to meet expectations with respect to any of the foregoing matters may have a negative effect on Forty Seven's stock price. Additional information concerning these and other risk factors affecting Forty Seven's business can be found in Forty Seven's periodic filings with theSecurities and Exchange Commissionatwww.sec.gov. These forward-looking statements are not guarantees of future performance and speak only as of the date hereof, and, except as required by law, Forty Seven disclaims any obligation to update these forward-looking statements to reflect future events or circumstances.

Forty SevenInvestors:Hannah Deresiewicz, (212) 362-1200hannah.deresiewicz@sternir.com

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Media:Sarah Plumridge, (312) 506-5218fortyseven@hdmz.com

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Forty Seven and Rocket Pharmaceuticals Announce Research Collaboration for Fanconi Anemia - BioSpace

Bone Marrow Stem Cells Comments Off on Forty Seven and Rocket Pharmaceuticals Announce Research Collaboration for Fanconi Anemia – BioSpace | March 12th, 2020

The College of Engineering for the first time has five faculty members who have been awarded National Science Foundations (NSF) Faculty Early Career Development (CAREER) grants. Four of the recipients of the five-year grants, Lauren B. Andrews,Peter J. Beltramo,Jungwoo Leeand Sarah L. Perry, are assistant proferssors in chemical engineering, while Xian Duis an assistant professor in mechanical and industrial engineering.

Sanjay Raman, dean of the College of Engineering, welcomed news of the grants. These awards are a testimony to the remarkable potential of these early-career UMass engineering faculty, he says. They are also the product of strong faculty development programs at the college and university levels, and outstanding mentorship by colleagues across the college. We look forward to the impactful research and educational innovations of these rising stars in emerging areas such as therapeutics and vaccine development, tissue engineering, biomanufacturing, biosensors and flexible electronics.

Du is the principal investigator on a $571,655 grant that focuses on improvements in roll-to-roll soft lithography. He is establishing a learning-based modeling method that guides the design and control of continuous microcontact printing processes and investigates continuous pattern formation mechanisms.

Andrews, the Marvin and Eva Schlanger Faculty Fellow in chemical engineering, will do researchstudying how communities of bacteria can be engineered to have coordinated behaviors. This will have numerous applications in biomanufacturing, cell-based therapies, and medical diagnostics. Andrewss $589,060 grant will fund research into developing a new approach for effectively programming how cells in a bacterial community work together in a predictive and highly controllable way.

Beltramos $592,332 grant will support his work on understanding the interplay between lipid composition and biomolecule transport in biological membranes. This is fundamental research that could enable the development of such breakthroughs as advanced drug delivery systems, biosensors, and other biomimetic materials.

Lee says his $549,710 grant will fund research that could lead to a greater understanding through which bone remodeling and blood forming processes are functionally coupled in porus, or trabecular bone cavities, by creating tissue engineered stem cell bone marrow models.

Perrys $657,920 grant will fund a study of a groundbreaking new approach to protein stabilization based on nature-inspired strategies. Her research has the ultimate goal of boosting the accessibility of vaccines and other therapeutics, especially in developing countries, and extending the reach of temperature-stable proteins to sensing and catalysis applications.

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Five College of Engineering Faculty Win NSF CAREER Grants - UMass News and Media Relations

Bone Marrow Stem Cells Comments Off on Five College of Engineering Faculty Win NSF CAREER Grants – UMass News and Media Relations | March 12th, 2020

PERTH, Australia Australian stem cell therapy company Mesoblast Ltd. plans to evaluate its allogeneic mesenchymal stem cell (MSC) candidate, remestemcel-L, in patients with acute respiratory distress syndrome (ARDS) caused by coronavirus (COVID-19) in the U.S., Australia, China and Europe.

The company is in active discussions with various governments, regulatory authorities, medical institutions and pharmaceutical companies to implement these activities.

What people are dying of is acute respiratory distress syndrome, which is the bodys immune response to the virus in the lungs, and the immune system goes haywire, and in its battle with the virus it overreacts and causes severe damage to the lungs, Mesoblast CEO Silviu Itescu told BioWorld.

Were going to be evaluating whether an injection of our cells intravenously can tone down the immune system just enough so it gets rid of the virus but doesnt destroy your lungs at the same time.

Recently published results from an investigator-initiated clinical study conducted in China reported that allogeneic MSCs cured or significantly improved functional outcomes in all seven treated patients with severe COVID-19 pneumonia.

We have now looked at our own data in lung disease in adults where half the patients had the same kind of inflammation in the lungs as you get with coronavirus, and our cells significantly reduced the inflammation and significantly improved lung function, Itescu said, noting that he is awaiting emergency use authorization to treat patients under a clinical trial protocol.

In a post-hoc analyses of a 60-patient randomized controlled study in chronic obstructive pulmonary disease (COPD), remestemcel-L infusions were well-tolerated, significantly reduced inflammatory biomarkers, and significantly improved pulmonary function in those patients with elevated inflammatory biomarkers.

Since the same inflammatory biomarkers are also elevated in COVID-19, those data suggest that remestemcel-L could be useful in the treatment of patients with ARDS due to COVID-19. The COPD study results have been submitted for presentation at an international conference, with full results to be submitted for publication shortly.

Mortality in COVID-19-infected patients with the inflammatory lung condition is reported to approach 50% and is associated with older age, co-morbidities such as diabetes, higher disease severity, and elevated markers of inflammation.

Current therapeutic interventions do not appear to be improving in-hospital survival, and remestemcel-L has potential for use in the treatment of ARDS, which is the principal cause of death in COVID-19 infection.

Itescu said he didnt know of any other stem cell companies that were doing this. He said that other companies could try the approach from a research perspective but that Mesoblast has all the patents locked down.

The companys intellectual property portfolio encompasses more than 1,000 patents or patent applications in all major markets and includes the use of MSCs obtained from any source for patients with ARDS, and for inflammatory lung disease due to coronavirus (COVID-19), influenza and other viruses.

Remestemcel-L is being studied in numerous clinical trials across several inflammatory conditions, including in elderly patients with lung disease and adults and children with steroid-refractory acute graft-vs.-host disease (aGVHD).

Mesoblasts stem cell therapy is currently being reviewed by the FDA for potential approval in the treatment of children with steroid-refractory aGVHD. The company submitted the final module of a rolling BLA in January.

Remestemcel-L is being developed for rare pediatric and adult inflammatory conditions. It is an investigational therapy comprising culture-expanded MSCs derived from the bone marrow of an unrelated donor and is administered in a series of intravenous infusions.

The stem cell therapy is believed to have immunomodulatory properties to counteract the inflammatory processes that are implicated in several diseases by down-regulating the production of pro-inflammatory cytokines, increasing production of anti-inflammatory cytokines, and enabling recruitment of naturally occurring anti-inflammatory cells to involved tissues, according to Mesoblast.

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Australia's Mesoblast plans to evaluate its stem cell therapy in patients infected with COVID-19 - BioWorld Online

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Graft-versus-host disease can occur any time after a transplant when donor bone marrow or stem cells attack the recipient

CytoDyn Inc (), a late-stage biotechnology company, said Wednesday that it has treated its first patient with its lead drug leronlimab (PRO 140), in its Phase 2 clinical trial for graft-versus-host disease (GvHD) under the modified trial protocol.

Graft-versus-host disease can occur at any time after a transplant. It is a rare condition that typically occurs when donor bone marrow or stem cells attack the recipient.

In a statement, the Vancouver, Washington-based company said the modified protocol now includes reduced intensity conditioning (RIC) patients and an open-label design under which all enrollees receive leronlimab. The modified protocol also provides for a 50% increase in the dose of leronlimab to more closely mimic preclinical dosing.

The next review of data by the independent data monitoring committee (IDMC) will occur after the enrollment of 10 patients under the amended protocol after each patient has been dosed for 30 days, said the company.

CytoDyn CEO Nader Pourhassan pointed out that GvHD is a life-threatening complication following bone marrow transplantation in patients with leukemia, who have compromised immune systems due to treatment with aggressive cancer therapies.

We selected GvHD as one of our immunology indications for leronlimab, as it targets and masks the CCR5 receptor on T cells. This receptor on T cells is an important mediator of inflammatory diseases including GvHD, especially in organ damage that is the most frequent cause of death in these patients, said Dr Pourhassan.

Based upon the compelling results in our preclinical studies, we are optimistic about the opportunities for leronlimab to provide a therapy for transplant patients to mitigate GvHD, he added.

A preclinical study by Dr Denis R Burger, CytoDyns former chief science officer, and Daniel Lindner, from the Department of Translational Hematology and Oncology Research, at The Cleveland Clinic, was published in the peer-reviewed journal called the Biology of Blood and Marrow Transplantation.

The US Food and Drug Administration earlier granted orphan drug designation to leronlimab for the prevention of GvHD. The designation provides CytoDyn with various incentives and benefits including seven years of US market exclusivity for leronlimab in GvHD, subject to FDA approval for use in this indication.

Leronlimab was earlier granted Fast Track status by the FDA for the treatment of HIV in combination with the cocktail known as highly active antiretroviral therapy (HAART), and for metastatic triple-negative breast cancer, a rare variety which doesnt respond to some treatments.

Leronlimab has completed nine clinical trials and has been given to 800 patients in HIV treatment programs, without a single drug-related serious adverse event. CytoDyn is developing leronlimab to battle multiple diseases. The company has also filed an IND application and a Phase 2 clinical trial protocol with the FDA to treat patients with NASH - damage caused by a build-up of fat in the liver.

Contact the author Uttara Choudhury at[emailprotected]

Follow her onTwitter:@UttaraProactive

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CytoDyn treats first patient with leronlimab in Phase 2 trial for GvHD under modified protocol - Proactive Investors USA & Canada

Bone Marrow Stem Cells Comments Off on CytoDyn treats first patient with leronlimab in Phase 2 trial for GvHD under modified protocol – Proactive Investors USA & Canada | March 10th, 2020

The second person ever to be cleared of HIV has revealed his identity, saying he wants to be an ambassador of hope to others with the condition.

Adam Castillejo, the so-called London patient, was declared free of HIV last year, 18 months after stopping antiretroviral therapy following a stem cell or bone marrow transplant to treat blood cancer.

Castillejo, 40, went public on Monday in an interview with the New York Times and revealed he had been living with HIV since 2003.

In 2012 he was diagnosed with acute myelogenous leukaemia and subsequently underwent a stem cell transplant. Crucially, the medical team picked a donor whose stem cells had two copies of a mutation that meant the white blood cells they developed into were resistant to HIV.

Timothy Brown, known as the Berlin patient and the first person to be cleared of the virus, underwent a similar treatment. However, while Brown and Castillejo had chemotherapy, only Brown had radiotherapy as part of his cancer treatment.

Last year it emerged the procedure had not only successfully treated the cancer, but that Castillejo was in remission for HIV as well. However, he chose to remain anonymous at the time.

I was watching TV and its like, OK, theyre talking about me, he told the New York Times. It was very strange, a very weird place to be.

Now Castillejo has decided to reveal his identity because he wants his case to be a cause for optimism. This is a unique position to be in, a unique and very humbling position, Castillejo said. I want to be an ambassador of hope.

Stem cell transplants are not suitable for most people with HIV because they involve a serious and invasive procedure that carries risks.

However, drug advances mean people who are HIV positive can take a pill every day to reduce their levels of the virus, preventing transmission and helping them to live a long and active life.

Prof Ravindra Gupta, the first author of the new study from Cambridge University, said Castillejos case was important: It is a second case of cure,. It means the first one wasnt an anomaly or a fluke.

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Second person ever to be cleared of HIV reveals identity - The Guardian

Bone Marrow Stem Cells Comments Off on Second person ever to be cleared of HIV reveals identity – The Guardian | March 10th, 2020

Bone remodeling and regeneration are dependent on resident stem/progenitor cells with the capability to replenish mature osteoblasts and repair the skeleton.

Until now, it has been thought that stem cells for bone lie within the bone marrow and the outer surface of the bone. Many studies have described the existence of a network of vascular channels that helped distribute blood cells out of the bone marrow. However, none of the studies had proved the existence of cells within these channels.

A new study by the scientists from the UConn School of Dental Medicine has discovered the population of stem cells that reside along the vascular channels within the cortical bone and have the ability to generate new bone. These stem cells stretch across the bone and connect the inner and outer parts of the bone.

Lead investigator Dr. Ivo Kalajzic, professor of reconstructive sciences, said, This is a discovery of perivascular cells residing within the bone itself that can generate new bone-forming cells. These cells likely regulate bone formation or participate in bone mass maintenance and repair.

This is the first study that reports the existence of these progenitor cells within the cortical bone that can generate new bone-forming cellsosteoblaststhat can be used to help remodel a bone.

To reach this conclusion, the scientists observed the stem cells within an ex vivo bone transplantation model. These cells migrated out of the transplant and started to reconstruct the bone marrow cavity and form new bone.

However, further study is required to determine the cells potential to regulate bone formation and resorption.

The study is presented in the journal Stem Cells.

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These new stem cells have the ability to generate new bone - Tech Explorist

Bone Marrow Stem Cells Comments Off on These new stem cells have the ability to generate new bone – Tech Explorist | March 9th, 2020

A year after the London Patient was introduced to the world as only the second person to be cured of H.I.V., he is stepping out of the shadows to reveal his identity: He is Adam Castillejo.

Six feet tall and sturdy, with long, dark hair and an easy smile, Mr. Castillejo, 40, exudes good health and cheer. But his journey to the cure has been arduous and agonizing, involving nearly a decade of grueling treatments and moments of pure despair. He wrestled with whether and when to go public, given the attention and scrutiny that might follow. Ultimately, he said, he realized that his story carried a powerful message of optimism.

This is a unique position to be in, a unique and very humbling position, he said. I want to be an ambassador of hope.

Last March, scientists announced that Mr. Castillejo, then identified only as the London Patient, had been cured of H.I.V. after receiving a bone-marrow transplant for his lymphoma. The donor carried a mutation that impeded the ability of H.I.V. to enter cells, so the transplant essentially replaced Mr. Castillejos immune system with one resistant to the virus. The approach, though effective in his case, was intended to cure his cancer and is not a practical option for the widespread curing of H.I.V. because of the risks involved.

Only one other individual with H.I.V. Timothy Ray Brown, the so-called Berlin Patient, in 2008 has been successfully cured, and there have been many failed attempts. In fact, Mr. Castillejos doctors could not be sure last spring that he was truly rid of H.I.V., and they tiptoed around the word cure, instead referring to it as a remission.

Still, the news grabbed the worlds attention, even that of President Trump.

And by confirming that a cure is possible, it galvanized researchers.

Its really important that it wasnt a one-off, it wasnt a fluke, said Richard Jefferys, a director at Treatment Action Group, an advocacy organization. Thats been an important step for the field.

For Mr. Castillejo, the experience was surreal. He watched as millions of people reacted to the news of his cure and speculated about his identity. I was watching TV, and its, like, OK, theyre talking about me, he said. It was very strange, a very weird place to be. But he remained resolute in his decision to remain private until a few weeks ago.

For one, his doctors are more certain now that he is virus-free. We think this is a cure now, because its been another year and weve done a few more tests, said his virologist, Dr. Ravindra Gupta of the University of Cambridge.

Mr. Castillejo also tested his own readiness in small ways. He set up a separate email address and telephone number for his life as LP, as he refers to himself, and opened a Twitter account. He began talking weekly with Mr. Brown, the only other person who could truly understand what he had been through. In December, Mr. Castillejo prepared a statement to be read aloud by a producer on BBC Radio 4.

After talking through his decision with his doctors, friends and mother, he decided the time was right to tell his story.

I dont want people to think, Oh, youve been chosen, he said. No, it just happened. I was in the right place, probably at the right time, when it happened.

Mr. Castillejo grew up in Caracas, Venezuela. His father was of Spanish and Dutch descent which later turned out to be crucial and served as a pilot for an ecotourism company. Mr. Castillejo speaks reverently of his father, who died 20 years ago, and bears a strong resemblance to him. But his parents divorced when he was young, so he was primarily raised by his industrious mother, who now lives in London with him. She taught me to be the best I could be, no matter what, he said.

As a young man, Mr. Castillejo made his way first to Copenhagen and then to London in 2002. He was found to have H.I.V., the virus that causes AIDS, in 2003.

I do recall when the person told me and the panic set in, he said. At the time, an H.I.V. diagnosis was often seen as a death sentence, and Mr. Castillejo was only 23. It was a very terrifying and traumatic experience to go through.

With the support of his partner at the time, Mr. Castillejo persevered. He turned the passion for cooking he had inherited from his grandmother into a job as a sous chef at a fashionable fusion restaurant. He adopted an unfailingly healthy lifestyle: He ate well, exercised often, went cycling, running and swimming.

Then, in 2011, came the second blow. Mr. Castillejo was in New York City, visiting friends and brunching on the Upper East Side, when a nurse from the clinic where he went for regular checkups called him. Where are you? she asked. When Mr. Castillejo told her, she would say only that they had some concerns about his health and that he should come in for more tests when he returned to London.

He had been experiencing fevers, and the tests showed that they were the result of a Stage 4 lymphoma. I will never forget my reaction as once again my world changed forever, he said. Once again, another death sentence.

Years of harsh chemotherapy followed. Mr. Castillejos H.I.V. status complicated matters. Each time his oncologists adjusted his cancer treatment, the infectious-disease doctors had to recalibrate his H.I.V. medications, said Dr. Simon Edwards, who acted as a liaison between the two teams.

There is little information about how to treat people with both diseases, and H.I.V.-positive people are not allowed to enter clinical trials. So with each new chemotherapy combination, Mr. Castillejos doctors were venturing further into unchartered territory, Dr. Edwards said.

With each treatment that seemed to work and then didnt, Mr. Castillejo fell into a deeper low. He saw fellow patients at the clinic die and others get better, while he kept returning, his body weakening with each round.

I was struggling mentally, he said. I try to look at the bright side, but the brightness was fading.

In late 2014, the extreme physical and emotional toll of the past few years caught up to Mr. Castillejo, and two weeks before that Christmas he disappeared. His friends and family imagined the worst, and filed a missing persons report. Mr. Castillejo turned up four days later outside London, with no memory of how he had ended up there or what he had done in the interim. He described it as switching off from his life.

Around that same time, he said, he felt so defeated that he also contemplated going to Dignitas, the Swiss company that helps terminally ill people take their own lives: I felt powerless. I needed control, to end my life on my own terms. He made it through that dark period, and emerged with a determination to spend whatever was left of his life fighting.

Still, in the spring of 2015, his doctors told him he would not live to see Christmas. A bone-marrow transplant from a donor is sometimes offered to people with lymphoma who have exhausted their other options, but Mr. Castillejos doctors did not have the expertise to try that, especially for someone with H.I.V.

His close friend, Peter, was not ready to give up, and together they searched online for alternatives. (Peter declined to reveal his last name because of privacy concerns.) They discovered that at a hospital in London was Dr. Ian Gabriel, an expert in bone-marrow transplants for treating cancer, including in people with H.I.V. Because of their last-ditch effort, Mr. Castillejo said, Were here today. You never, never know.

Within a week, he met with Dr. Gabriel, who tried a third and final time to tap Mr. Castillejos own stem cells for a transplant. When that failed, Dr. Gabriel explained that Mr. Castillejos Latin background might complicate the search for a bone-marrow donor who matched the genetic profile of his immune system. To everyones surprise, however, Mr. Castillejo quickly matched with several donors, including a German one perhaps a legacy from his half-Dutch father who carried a crucial mutation called delta 32 that hinders H.I.V. infection. A transplant from this donor offered the tantalizing possibility of curing both Mr. Castillejos cancer and the H.I.V.

When Dr. Gabriel called with the news in the fall of 2015, Mr. Castillejo was on the top deck of one of Londons iconic red buses, on his way to see his general practitioner for a checkup. His thoughts raced alongside the scenery: He had only recently been told he was going to die, and now he was being told he might be cured of both cancer and H.I.V.

I was trying to digest what just happened, he recalled. But after that call, I had a big smile on my face. Thats where the journey began as LP.

With the possibility of an H.I.V. cure, the case immediately took on intense importance for everyone involved. Dr. Edwards, who had cared for Mr. Castillejo since 2012, had, as a young doctor in the early 1990s, seen many men his age die of H.I.V. What a privilege it would be to go from no therapy to a complete cure in my lifetime, he recalled telling Mr. Castillejo. So you have to get better no pressure.

Dr. Edwards involved Dr. Gupta, his former colleague and one of the few virologists in London he knew to be doing H.I.V. research. Dr. Gupta initially was skeptical; the approach had worked only once, 12 years earlier, with Mr. Brown. But Dr. Gupta also knew that the payoff could be huge. Antiretroviral drugs can suppress the virus to undetectable levels, but any interruption in the treatment can bring the virus roaring back, so a cure for H.I.V. is still the ultimate goal.

Dr. Gupta began carefully monitoring Mr. Castillejos H.I.V. status. In late 2015, Mr. Castillejo was preparing to receive the transplant when another major setback arose. His viral load shot back up with H.I.V. that appeared to be resistant to the drugs he had been taking.

This gave Dr. Gupta a rare glimpse at the typically suppressed virus, and allowed him to confirm that the viral strain was one that would be cleared by the transplant. But it also delayed the transplant by several months while the doctors adjusted Mr. Castillejos medications. He eventually received the transplant on May 13, 2016.

The next year was punishing. Mr. Castillejo spent months in the hospital. He lost nearly 70 pounds, contracted multiple infections and underwent several more operations. He had some hearing loss and began wearing a hearing aid. His doctors fretted over how to get his H.I.V. pills into his ulcer-filled mouth by crushing and dissolving them, or by feeding them to him through a tube. One of the doctors came to me and said to me, You must be very special, because I have more than 40 doctors and clinicians discussing your medication, Mr. Castillejo recalled.

Even after he left the hospital, the only exercise he initially was allowed to do was walking, so he walked for hours around the trendy Shoreditch neighborhood. He went to the flower market there every Sunday, treated himself to salted beef beigels to celebrate small successes and admired the colorful murals and vintage clothes.

A year on, as he became stronger, he slowly began thinking about forgoing the H.I.V. medications to see if he was rid of the virus. He took his last set of antiretroviral drugs in October 2017. Seventeen months later, in March 2019, Dr. Gupta announced the news of his cure.

Neither he nor Mr. Castillejo was prepared for what came next. Dr. Gupta found himself presenting the single case to a standing-room-only crowd at a conference, and shaking hands afterward with dozens of people. Mr. Castillejo was overwhelmed by the nearly 150 media requests to reveal his identity, and began to see a role he might play in raising awareness of cancer, bone-marrow transplants and H.I.V.

He has enrolled in several studies to help Dr. Gupta and others understand both diseases. So far, his body has shown no evidence of the virus apart from fragments the doctors call fossils and what seems to be a long-term biological memory of having once been infected.

Others in the H.I.V. community are reassured by this news, but expressed concern for Mr. Castillejos privacy and mental health.

It can be very important for people to have these kinds of beacons of hope, Mr. Jefferys, the Treatment Action Group director, said. At the same time, thats a lot of weight for someone to carry.

Mr. Castillejos friends have similar worries. But he is as ready as he will ever be, he said. He sees LP as his work identity and is determined to live his private life to its fullest. Having lost his lustrous dark hair several times over, he has now grown it to shoulder length. He has always enjoyed adventures, and with careful preparation he has begun traveling again, describing himself to fellow travelers only as a cancer survivor. He celebrated his 40th birthday with a trip to Machu Picchu, in Peru.

But in conversations about his status as the second person ever to be cured of H.I.V., Mr. Castillejo still adamantly refers to himself as LP, not Adam. When you call me LP, it calms me down, he said. LP to my name, that is kind of a big step.

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The London Patient, Cured of H.I.V., Reveals His Identity - The New York Times

Bone Marrow Stem Cells Comments Off on The London Patient, Cured of H.I.V., Reveals His Identity – The New York Times | March 9th, 2020

Steven Hodi Jr., the i3 Centers other PI, and director of Melanoma Center and the Center for Immuno-Oncology at Dana-Farber, and professor of medicine at Harvard Medical School (HMS), is leading the clinical cancer vaccine trial. He has been at the forefront of developing cancer immunotherapies using immune checkpoint inhibitors, a class of drugs able to re-activate tumor-destroying T cells that are muted in the tumor microenvironment. The funding for this center provides a unique opportunity to unite key investigators for translating fundamental advancements in immunology and biomedical engineering into highly synergistic approaches to improve the treatments for cancer patients, said Hod

Using both in vivo and ex vivo biomaterials-based approaches, the i3 Center aims to boost tumor-specific activities of cytotoxic T cells, by boosting different stages of the normal process by which T cells develop, and acquire anti-cancer activity. T cells normal development starts in the bone marrow where hematopoietic stem cells generate T cell progenitor cells. These migrate to the thymus to differentiate into nave T cells, which then travel further to lymph nodes. There, they encounter cancer-derived antigens presented to them by specialized antigen-presenting cells (APCs) that can activate T cells to recognize and eliminate cancer cells.

In relation to adoptive T cell therapies in which T cells are given to patients to fight their cancers, one team at the i3 Center will be led by Dana-Farber researchers Catherine J. Wu and Jerome Ritz, who along with Mooney, will develop and test biomaterials that can better mimic normal APCs in activating and directing the function of patient-derived T cells outside the human body, prior to their transplantation. Wu is chief of the Division of Stem Cell Transplantation and Cellular Therapies, and Ritz is executive director of the Connell and OReilly Families Cell Manipulation Core Facility at Dana-Farber.

We need to make efforts to enhance the ability of theimmune systemto recognizetumor cells. One directionmylaboratoryis taking makes use of innovative biomaterialsto help us to efficiently expandpolyclonaltumor-specificfunctionally-effectiveT cellsex vivoin a way that can be readily translated to theclinical setting. In our studies, we are currently focusing on melanoma and acute myeloid leukemia, said Wu, whose research interests include understanding the basis of effective human anti-tumor responses, including the identification and targeting of the tumor-specific antigens.

A second project explores the use of DNA origami, biocompatible nanostructures composed of DNA, to create cancer vaccines. DNA origami could provide significant advantages in presenting tumor-specific antigens and immune-enhancing adjuvants to APCs because the concentrations, ratios, and geometries of all components can be modulated with nano-scale precision to determine configurations that are more effective than other vaccination strategies. The project will be run by Wyss Institute Core Faculty member William Shih, Derin Keskin, lead immunologist at Dana-Farbers Translational Immunogenomics Lab, and Mooney.

In a third project, David Scadden, professor at Harvards Department of Stem Cell and Regenerative Biology, will collaborate with Mooney to build on their previous work. They will engineer biomaterials that recreate key features of the normal hematopoietic stem cell niche in the bone marrow. Such implantable biomaterials could help rapidly amplify T cell progenitor cells, and enhance T cell-mediated anti-cancer immunity. Scadden also is the Gerald and Darlene Jordan Professor of Medicine at Harvard University, and co-director of the Harvard Stem Cell Institute.

The i3 Centers investigators anticipate that it will stimulate additional cross-disciplinary concepts and research, due to the culture of continuous interactions, sharing of findings, data and samples between all investigators, as well strong biostatistical expertise provided by Donna Neuberg, a senior biostatistician broadly involved with exploring immune-modulating cancer interventions at the Dana-Farber.

This new i3 Center for cancer immunotherapy innovation really embodies how the Wyss Institute with its unparalleled capabilities in bioengineering and serving as a site for multidisciplinary collaboration, and can liaise with clinicians and researchers at our collaborating institutions to confront major medical problems and bring about transformative change, said Wyss Founding Director Donald Ingber. He is also theJudah Folkman Professor of Vascular Biologyat HMS and the Vascular Biology Program at Boston Childrens Hospital, and Professor of Bioengineering at SEAS.

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NIH-funded i3 Center formed to advance cancer immunotherapy - Harvard Gazette

Bone Marrow Stem Cells Comments Off on NIH-funded i3 Center formed to advance cancer immunotherapy – Harvard Gazette | March 8th, 2020