Scientists using a new motor neuron disease (MND) model have shown astrocytes may protect neurons from toxic TDP-43 protein aggregates in the early stages of disease.

Researchers have discovered that astrocytes can protect motor neurons in the central nervous system (CNS) from the toxicity of misfolded protein, TDP-43, in sporadic motor neuron disease (MND). The team suggest this rescue mechanism could be harnessed to slow disease progression, particularly in amyotrophic lateral sclerosis (ALS).

The study, published in Brain, demonstrated that this neurodegenerative disease is caused by accumulation of TDP-43 in motor neurons, resulting in cell death. However, the scientists noted that TDP-43 accumulation in neural support cells, called astrocytes, does not cause death. Instead they appear comparatively resistant.

According to the paper, when the two cell types are together, astrocytes protect motor neurons from the protein aggregates, promoting their survival. The researchers from the Francis Crick Institute and University College London, both UK, suggest that these cells may therefore be supporting motor neurons early on in sporadic MND. They called this a rescue mechanism.

when the two cell types are together, astrocytes protect motor neurons from the protein aggregates, promoting their survival

The role astrocytes have played in dealing with toxic forms of TDP-43 in motor neurons has not been previously well documented in motor neuron disease. Its exciting that weve now found that they may play an important protective role in the early-stages of this disease, explains Phillip Smethurst, lead author and former postdoc in the Human Stem Cells and Neurodegeneration Laboratory at the Crick. This has huge therapeutic potential finding ways to harness the protective properties of astrocytes could pave the way to new treatments. This could prolong their rescue function or find a way to mimic their behaviour in motor neurons so that they can protect themselves from the toxic protein.

In order to conduct this research, the team created a new model for MND, which more closely resembles the disease in patients. In the model they took healthy adult stem cells and exposed them to the toxic TPD-43 protein using post-mortem spinal cord tissue samples donated by patients with MND.

For the first time, we have been able to create a model of sporadic motor neuron disease by essentially transferring the toxic TDP-43 protein from post-mortem tissue into healthy human stem cell-derived motor neurons and astrocytes in order to understand how each cell type responds to this insult, both in isolation and when mixed together, said Dr Rickie Patani, co-senior author, group leader of the Human Stem Cells and Neurodegeneration Laboratory at the Crick and Professor of Human Stem Cells and Regenerative Neurology at UCL Queen Square Institute of Neurology.

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Astrocytes could be harnessed to protect motor neurons in MND - Drug Target Review

Spinal Cord Stem Cells Comments Off on Astrocytes could be harnessed to protect motor neurons in MND – Drug Target Review | February 11th, 2020

Methionine is an amino acid found in meat, eggs, and dairy. Its absorbed by T-cells that are part of our immune system. Those cells are also believed to be the immune cells that attack our myelin, creating the nerve damage that results in multiple sclerosis.

In this study, mice eating less methionine had a reduced number of a certain type of T-cell, which led to a delay in disease onset and progression. The researchers believe reducing methionine intake can actually dampen the immune cells that cause disease, leading to better outcomes.

Changing a persons diet to reduce the amount of methionine (amino acid found in food) could delay the development and progression of inflammatory and autoimmune disorders, including multiple sclerosis (MS).

That finding was described in the study Methionine Metabolism Shapes T Helper Cell Responses through Regulation of Epigenetic Reprogramming, published recently in the journal Cell Metabolism.

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***

Unlike hematopoietic stem cell transplants, in which stem cells are removed from a patients bone marrow and later infused back into the bloodstream, mesenchymal stem cell transplants (MSCT) collect those stem cells from the patients spinal column and return them there. This study concludes that MSCT is safe and that cells delivered into the spinal cord produced a significantly slower disease progression rate than did cells delivered into the bloodstream.

Transplanting patients ownmesenchymal stem cellsis a safe therapeutic approach and can delay disease progression in people with MS, a meta-analysis review shows.

The study also showed that cells transplanted to the spinal cord (intrathecal injection) were associated with significantly slower disease progression rates, compared to cells delivered into the bloodstream.

Click here to read the full story.

***

Why do neurologists often use spinal taps when determining whether someone has MS? This study provides one of the reasons.

People with MS have a more diverse set of immune cells in their cerebrospinal fluid (CSF), the fluid that bathes the central nervous system, but no such diversity is seen in their blood, a study reports. Instead, MS causes changes in the activation of immune cells in the blood.

The distinct set of immune cells in MS patients CSF shows enrichment of pro-inflammatory cells that promote disease severity in MS mouse models.

Click here to read the full story.

***

Heres encouraging news about a possible treatment that can lower the number of brain lesions in someone with MS. Keep in mind this is only a Phase 2 trial. A Phase 3 trial isnt expected until later this year. However, a news release from research sponsor Sanofisays, This molecule may be the first B-cell-targeted MS therapy that not only inhibits the peripheral immune system, but also crosses the blood-brain barrier to suppress immune cells that have migrated into the brain.

The experimental BTK inhibitor SAR442168 showed an acceptable safety profile and met its primary endpoint a significant reduction in the number of new lesions visible on a brain imaging scan in a Phase 2 trial in people with MS, study results show.

SAR442168, formerly known as PRN2246, is an oral, small molecule being co-developed by Principia Biopharmaand Sanofi Genzyme. It works by inhibiting Brutons tyrosine kinase (BTK), a protein important for the proliferation of immune cells, particularly B-cells. By blocking BTK, it is expected that SAR442168 can reduce inflammation that damages the nervous system in people with MS.

Click here to read the full story.

Did you know that some of my columns from The MS Wire are now available as audio briefings? You can listen to them here.

***

Note: Multiple Sclerosis News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The opinions expressed in this column are not those of Multiple Sclerosis News Today or its parent company, BioNews Services, and are intended to spark discussion about issues pertaining to multiple sclerosis.

Ed Tobias is a retired broadcast journalist. Most of his 40+ year career was spent as a manager with the Associated Press in Washington, DC. Tobias was diagnosed with Multiple Sclerosis in 1980 but he continued to work, full-time, meeting interesting people and traveling to interesting places, until retiring at the end of 2012.

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MS News that Caught My Eye Last Week: Methionine, MSCT, Spinal... - Multiple Sclerosis News Today

Spinal Cord Stem Cells Comments Off on MS News that Caught My Eye Last Week: Methionine, MSCT, Spinal… – Multiple Sclerosis News Today | February 10th, 2020

SpringWorks Therapeutics (NASDAQ:SWTX) and Neuralstem (NASDAQ:CUR) are both small-cap medical companies, but which is the better business? We will contrast the two companies based on the strength of their profitability, dividends, institutional ownership, valuation, earnings, analyst recommendations and risk.

Analyst Recommendations

This is a summary of recent ratings and recommmendations for SpringWorks Therapeutics and Neuralstem, as reported by MarketBeat.

SpringWorks Therapeutics presently has a consensus target price of $35.50, indicating a potential upside of 7.51%. Given SpringWorks Therapeutics higher possible upside, analysts clearly believe SpringWorks Therapeutics is more favorable than Neuralstem.

Profitability

This table compares SpringWorks Therapeutics and Neuralstems net margins, return on equity and return on assets.

Insider and Institutional Ownership

72.2% of SpringWorks Therapeutics shares are owned by institutional investors. Comparatively, 38.3% of Neuralstem shares are owned by institutional investors. 5.4% of Neuralstem shares are owned by company insiders. Strong institutional ownership is an indication that endowments, large money managers and hedge funds believe a company is poised for long-term growth.

Valuation and Earnings

This table compares SpringWorks Therapeutics and Neuralstems revenue, earnings per share (EPS) and valuation.

SpringWorks Therapeutics has higher earnings, but lower revenue than Neuralstem.

Summary

SpringWorks Therapeutics beats Neuralstem on 6 of the 8 factors compared between the two stocks.

SpringWorks Therapeutics Company Profile

SpringWorks Therapeutics, Inc., a clinical-stage biopharmaceutical company, acquires, develops, and commercializes medicines for underserved patient populations suffering from rare diseases and cancer. Its advanced product candidate is nirogacestat, an oral small molecule gamma secretase inhibitor that is in Phase 3 clinical trials for the treatment of desmoid tumors. The company is also developing mirdametinib, an oral small molecule MEK inhibitor that is in Phase 2b clinical trials for the treatment of neurofibromatosis type 1-associated plexiform neurofibromas; and Nirogacestat + belantamab mafodotin, which is in Phase 1b clinical trials for the treatment of relapsed or refractory multiple myeloma. In addition, it is developing Mirdametinib + lifirafenib, a combination therapy that is in Phase 1b clinical trials in patients with advanced or refractory solid tumors; and BGB-3245, an investigational oral selective small molecule inhibitor of specific BRAF driver mutations and genetic fusions, which is in preclinical studies in a range of tumor models with BRAF mutations or fusions. The company has collaborations with BeiGene, Ltd. and GlaxoSmithKline plc to develop combination approaches with nirogacestat and mirdametinib, as well as other standalone medicines. SpringWorks Therapeutics, Inc. was founded in 2017 and is headquartered in Stamford, Connecticut.

Neuralstem Company Profile

Neuralstem, Inc., a clinical stage biopharmaceutical company, focuses on the research and development of nervous system therapies based on its proprietary human neuronal stem cells and small molecule compounds. The company's stem cell based technology enables the isolation and expansion of human neural stem cells from various areas of the developing human brain and spinal cord enabling the generation of physiologically relevant human neurons of various types. Its lead product candidate is NSI-189, a chemical entity, which has been completed Phase II clinical trial for the treatment of major depressive disorder, as well as is in preclinical study for the treatment-refractory depression, Angelman Syndrome, Alzheimer's disease, ischemic stroke, diabetic neuropathy, irradiation-induced cognitive deficit, and long-term potentiation enhancement. The company also develops NSI-566, which has completed Phase II clinical trial for treating amyotrophic lateral sclerosis disease; Phase II clinical trial for the treatment of chronic ischemic stroke; and Phase I clinical trials for the treatment of chronic spinal cord injury, as well as is in preclinical study for the traumatic brain injury. In addition, it develops NSI-532, which is in preclinical study for treatment of Alzheimer's disease; and NSI-777 that is in preclinical study for treatment of human demyelinating diseases. Neuralstem, Inc. was founded in 1996 and is headquartered in Germantown, Maryland.

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Contrasting Neuralstem (NASDAQ:CUR) and SpringWorks Therapeutics (NASDAQ:SWTX) - Riverton Roll

Spinal Cord Stem Cells Comments Off on Contrasting Neuralstem (NASDAQ:CUR) and SpringWorks Therapeutics (NASDAQ:SWTX) – Riverton Roll | February 9th, 2020

Autolus Therapeutics (NASDAQ:AUTL) and Neuralstem (NASDAQ:CUR) are both small-cap medical companies, but which is the better business? We will compare the two companies based on the strength of their profitability, analyst recommendations, dividends, earnings, risk, valuation and institutional ownership.

Profitability

This table compares Autolus Therapeutics and Neuralstems net margins, return on equity and return on assets.

Insider & Institutional Ownership

26.6% of Autolus Therapeutics shares are owned by institutional investors. Comparatively, 38.3% of Neuralstem shares are owned by institutional investors. 5.4% of Neuralstem shares are owned by insiders. Strong institutional ownership is an indication that large money managers, endowments and hedge funds believe a company will outperform the market over the long term.

Earnings & Valuation

This table compares Autolus Therapeutics and Neuralstems gross revenue, earnings per share and valuation.

Neuralstem has lower revenue, but higher earnings than Autolus Therapeutics.

Risk and Volatility

Autolus Therapeutics has a beta of 0.88, suggesting that its stock price is 12% less volatile than the S&P 500. Comparatively, Neuralstem has a beta of 1.81, suggesting that its stock price is 81% more volatile than the S&P 500.

Analyst Ratings

This is a summary of current ratings and recommmendations for Autolus Therapeutics and Neuralstem, as provided by MarketBeat.

Autolus Therapeutics currently has a consensus target price of $25.00, suggesting a potential upside of 155.10%. Given Autolus Therapeutics higher probable upside, equities analysts plainly believe Autolus Therapeutics is more favorable than Neuralstem.

Summary

Autolus Therapeutics beats Neuralstem on 7 of the 11 factors compared between the two stocks.

About Autolus Therapeutics

Autolus Therapeutics plc, a biopharmaceutical company, develops T cell therapies for the treatment of cancer. The company is developing AUTO1, a CD19-targeting programmed T cell therapy, which is in Phase I trial to reduce the risk of severe cytokine release syndrome; AUTO2, a dual-targeting programmed T cell therapy that is in Phase I/II clinical trial for the treatment of relapsed or refractory multiple myeloma; and AUTO3, a dual-targeting programmed T cell therapy, which is in Phase I/II clinical trials for treating relapsed or refractory diffuse large B-cell lymphoma. It is also developing AUTO4, a programmed T cell therapy that is in Phase I/II clinical trial for the treatment of peripheral T-cell lymphoma; and AUTO6, a programmed T cell therapy for treating neuroblastoma. Autolus Therapeutics plc has a collaboration partnership with AbCellera Biologics Inc. on antibody discovery project. The company was founded in 2014 and is headquartered in London, the United Kingdom.

About Neuralstem

Neuralstem, Inc., a clinical stage biopharmaceutical company, focuses on the research and development of nervous system therapies based on its proprietary human neuronal stem cells and small molecule compounds. The company's stem cell based technology enables the isolation and expansion of human neural stem cells from various areas of the developing human brain and spinal cord enabling the generation of physiologically relevant human neurons of various types. Its lead product candidate is NSI-189, a chemical entity, which has been completed Phase II clinical trial for the treatment of major depressive disorder, as well as is in preclinical study for the treatment-refractory depression, Angelman Syndrome, Alzheimer's disease, ischemic stroke, diabetic neuropathy, irradiation-induced cognitive deficit, and long-term potentiation enhancement. The company also develops NSI-566, which has completed Phase II clinical trial for treating amyotrophic lateral sclerosis disease; Phase II clinical trial for the treatment of chronic ischemic stroke; and Phase I clinical trials for the treatment of chronic spinal cord injury, as well as is in preclinical study for the traumatic brain injury. In addition, it develops NSI-532, which is in preclinical study for treatment of Alzheimer's disease; and NSI-777 that is in preclinical study for treatment of human demyelinating diseases. Neuralstem, Inc. was founded in 1996 and is headquartered in Germantown, Maryland.

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Head to Head Review: Autolus Therapeutics (NASDAQ:AUTL) and Neuralstem (NASDAQ:CUR) - Riverton Roll

Spinal Cord Stem Cells Comments Off on Head to Head Review: Autolus Therapeutics (NASDAQ:AUTL) and Neuralstem (NASDAQ:CUR) – Riverton Roll | February 8th, 2020

Hip replacements, severe burns, spinal cord injuries, blast injuries, traumatic brain injuriesthese seemingly disparate traumas can each lead to a painful complication during the healing process called heterotopic ossification. Heterotopic ossification is abnormal bone formation within muscle and soft tissues, an unfortunately common phenomenon that typically occurs weeks after an injury or surgery. Patients with heterotopic ossification experience decreased range of motion, swelling and pain.

Currently, theres no way to prevent it and once its formed, theres no way to reverse it, says Benjamin Levi, M.D., Director of the Burn/Wound/Regeneration Medicine Laboratory and Center for Basic and Translational Research in Michigan Medicines Department of Surgery. And while experts suspected that heterotopic ossification was somehow linked to inflammation, new U-M research explains how this happens on a cellular scaleand suggests a way it can be stopped.

To help explain how the healing process goes awry in heterotopic ossification, the research team, led by Levi, Michael Sorkin, M.D. and Amanda Huber, Ph.D., of the Department of Surgerys section of plastic surgery, took a closer look at the inflammation process in mice. Using tissue from injury sites in mouse models of heterotopic ossification, they used single cell RNA sequencing to characterize the types of cells present. They confirmed that macrophages were among the first responders and might be behind aberrant healing.

Macrophages are white blood cells whose normal job is to find and destroy pathogens. Upon closer examination, the Michigan team found that macrophages are more complex than previously thoughtand dont always do what they are supposed to do.

Macrophages are a heterogenous population, some that are helpful with healing and some that are not, explains Levi. People think of macrophages as binary (M1 vs. M2). Yet weve shown that there are many different macrophage phenotypes or states that are present during abnormal wound healing.

Specifically, during heterotopic ossification formation, the increased presence of macrophages that express TGF-beta leads to an errant signal being sent to bone forming stem cells.

For now, the only way to treat heterotopic ossification is to wait for it to stop growing and cut it out which never completely restores joint function. This new research suggests that there may be a way to treat it at the cellular level. Working with the lab led by Stephen Kunkel, Ph.D. of the Department of Pathology, the team demonstrated that an activating peptide to CD47, p7N3 could alter TGF-beta expressing macrophages, reducing their ability to send signals to bone-forming stem cells that lead to heterotopic ossification.

During abnormal wound healing, we think there is some signal that continues to be present at an injury site even after the injury should have resolved, says Levi. Beyond heterotopic ossification, Levi says the studys findings can likely be translated to other types of abnormal wound healing like muscle fibrosis.

The team hopes to eventually develop translational therapies that target this pathway and further characterize not just the inflammatory cells but the stem cells responsible for the abnormal bone formation.

The paper is published in the journal Nature Communications. Other U-M authors include: Charles Hwang, William Carson IV, Rajarsee Menon, John Li, Kaetlin Vasquez, Chase Pagani, Nicole Patel, Shuli Li, Noelle D. Visser, Yashar Niknafs, Shawn Loder, Melissa Scola, Dylan Nycz, Katherine Gallagher, Laurie K. McCauley, Shailesh Agarwal, and Yuji Mishina.

Paper Cited: Regulation of heterotopic ossification by monocytes in a mouse model of aberrant wound healing, Nature Communications, DOI: 10.1038/s41467-019-14172-4

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Abnormal Bone Formation After Trauma Explained and Reversed in Mice - Michigan Medicine

Spinal Cord Stem Cells Comments Off on Abnormal Bone Formation After Trauma Explained and Reversed in Mice – Michigan Medicine | February 6th, 2020

It happens whenever there are news stories about a new treatment claiming to cure paralysis.

I get flooded with messages from distant relatives, or people I went to high school with but haven't seen in 10 years.

"OMG YOU TOTALLY NEED TO DO THIS."

I'm not saying other people shouldn't try whatever treatments they want to, but for me, there's too little certainty and too many unknown factors.

After 15 years in a wheelchair, I've gained the perspective that walking, in fact, does not equate happiness.

I'll never forget the metaphor used to explain to me how one would repair a spinal cord, even if I was a little high on morphine when I heard it.

I was 16, laying in a hospital bed with four large screws drilled into my skull to stabilize my spine.

"Imagine squeezing all of the toothpaste out of a tube. Now try and get that toothpaste back into the tube without changing it's shape or structure. That's how fragile your spinal cord is."

Sounds impossible, right? Maybe. Or maybe the technology just hasn't been invented yet.

The thing no one tells you about having a spinal cord injury is that not walking is the easiest adjustment. You don't need to check your eyes. You read that right.

The human body and muscle memory are pretty adaptable. Using a wheelchair is the easy part.

First, there are societal stigmas. They could fill their own novel.

Every person with a disability has a few horror stories. Personally, I applied to more than 600 jobs before getting a part-time, entry-level position. Shout out to the YMCA of Saskatoon for giving me a shot when no one else would!

Another thing that doesn't often get talked about is the secondary health issues that come along with a spinal cord injury. Low blood pressure, autonomic dysreflexia, inability to regulate your body temperature, bowel and bladder problems, and pressure sores to name a few.

These are the really hard parts.

These secondary health issues are why I have no interest in an epidural stimulation implant or any other elective surgery of that nature. I know it's exciting to see someone moving their leg after an injury or walking while assisted, but the truth is we don't know what other unknown factors such treatments might present.

I've seen plenty of stories about possible "cures." When I was first injured it was stem cells, then embryonic stem cells, then there were the paralyzed rats learning to walk again.

Every few years there's a new procedure that makes a splash. Everyone is positive that this time, this procedure, this one is the cure. None have come to fruition.

Hope and optimism are vital, but there's a fine line between hope and false hope. I've seen far too many people unable to overcome the false hope and remain bitter and angry that they can't be "normal."

The thing is, moving my leg or even walking (although it would be cool) wouldn't change the functional quality of my life. I'm already independent. I'm already quite happy with my life. Gaining the ability to move a leg still wouldn't address those secondary health issues.

I'm not saying any of these potential treatments aren't amazing advancements in medicine, but if you can't guarantee me the ability to sweat so I don't overheat in our prairie summers, or control of my bowels or bladder, it's not worth the unknowns or cost at this point in my life.

There's no guarantee. I won't compromise for a maybe.

This column is part of CBC'sOpinionsection. For more information about this section, please read thiseditor's blogand ourFAQ.

Interested in writing for us? We accept pitches for opinion and point-of-view pieces from Saskatchewan residents who want to share their thoughts on the news of the day, issues affecting their community or who have a compelling personal story to share. No need to be a professional writer!

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Yes, I've seen the stories about that new spinal treatment. Here's why I'm not interested - CBC.ca

Spinal Cord Stem Cells Comments Off on Yes, I’ve seen the stories about that new spinal treatment. Here’s why I’m not interested – CBC.ca | February 5th, 2020

Spinal cord injuries can result in severe neurological dysfunction, including motor, sensory, and autonomic paralysis, and up until now there has been no cure or effective treatment for such injuries.

But the first human trial based on Nobel Prize winning induced pluripotent stem cells (IPSC) technology, is due to start in Japan, giving hope to hundreds of thousands of paralysed patients, that there might be light at the end of their tunnel.

The spinal cord is responsible for relaying signals up and down the body from the brain to the nervous system. The spinal cord is a bundle of nerves contained in the spinal canal, which is cocooned in the spinal column (not to be confused with the spinal cord they are two very separate entities).

The spinal cord itself has a protective sheath wrapped around it which acts as insulation whilst allowing nerve signals from the brain to travel even faster to where they need to go.

The spinal column is divided into five distinct sections:

The site of the spinal cord injury will determine the severity of the injury and injuries are classified as either:

The higher up the spinal cord the injury occurs, the more function and feeling will be lost. It is estimated that approximately every year there are between 8 to 246 cases per million incidences of spinal cord injuries worldwide.

Stem cell therapy is amongst the most exciting ongoing research for people with spinal cord injuries, in modern medicine. Because whilst the research is still in its infancy, legitimate trials are showing promising results.

According to the Journal of the American Academy of Orthopedic Surgeons, there are different stem cells which have varying abilities to restore certain functions.

Stem cells are self-renewing cells that can differentiate into one or more specific cell types. For people with spinal cord injuries, stem cells could prevent further cell death, stimulate cell growth from the existing cells and even replace the injured cells, restoring the communication channels between the body and the brain.

Until recently, stem cell research has involved looking at:

It is research into these induced pluripotent stem cells that the team in Japan are currently laying down the groundwork for. They are planning to conduct a first-in-human study of an induced pluripotent stem cell-based intervention, for subacute spinal cord injury.

Not only that, but it is the first such therapy to look into treating this kind of injury, that has ever received government approval for sale to patients.

However there are concerns by those who work in the field, but arent working on this particular project, that the evidence to support the suggestion that the treatment works, is insufficient. They state that the approval for the research was based on a small, poorly designed clinical trial.

Like the majority of scientific breakthroughs that have gone before, there will always be naysayers we used to think the world was flat and the sun orbited Earth, that the body was composed of four humours and an imbalance in those made us sick.

Those theories were disproved, and look how far weve come since then. Now imagine if we could make a paralysed person walk again. It will happen. But for now, lets celebrate and support this team for trying.

Because whilst there have been multiple attempts to develop stem cell transplantation approaches with the aim to regenerate damaged spinal cords before, this multicentre team is planning the first that might actually work, and be ethical to boot.

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Stem Cell Regeneration for Spinal Cord injuries

Spinal Cord Stem Cells Comments Off on Stem Cell Regeneration for Spinal Cord injuries | February 4th, 2020

SAN ANTONIO, Feb. 3, 2020 /PRNewswire/ -- SASpine is now offering cutting edge Stem Cell Treatments to patients. For the past several years Dr. Steven Cyr, Mayo Clinic Trained Spine Surgeon, has been researching the benefits of stem cells in the treatment of multiple medical conditions including spinal disorders, specifically, conditions which involve spinal cord injury, degenerative disc disease, herniated discs, and as a supplement to enhance the success of Spinal fusions when treating instability, deformity, and fractures of the spine.

Steven J. Cyr, M.D., is a spine surgeon who has gained a reputation for surgical excellence in Texas, throughout the nation, and abroad.

Dr. Steven Cyr has been treating patients using growth factors and stem cells contained in amniotic tissue and bone marrow aspirate to provide a potential for improved success with fusion procedures, when treating herniated discs, and for arthritic or damaged joints, with remarkable success. "The goal of any medical intervention is to yield improved outcomes with the ideal result of returning a patient to normal function, when possible," states Dr Cyr. He went on to elaborate that there are times when only a structural solution can solve problems related to spinal disorders, but even in that scenario, the use of stem cells or growth factors derived from stem cell products can possibly improve the success of surgical procedures. "I have patients previously unable to jog or run return to normal function and athletic ability after injections of growth factors and stem cell products into the knee joints, hip joints, and shoulder joints," he said. "This includes high-level athletes, professional dancers, and the average weekend warrior."

There may be promise in treating patients with spinal cord injury as well. SASpine CEO, LeAnn Cyr, states, "There are reports of patients gaining significant neurological improvement after being treated with stem cells." Dr Cyr continues, "Most patients with spinal cord injuries resulting from trauma also have mechanical pressure on the nerves that result either from bone fragments or disc material compressing the spinal cord that needs to be removed along with surgical stabilization of the spinal bones. There's significant potential that stem cells bring to the equation when treating these types of patients, and I am excited about the potential that these products offer to the host of treatments to address spinal conditions and arthritic joints."

For more information about SASpine's Stem Cell Treatment Program, visit http://www.saspine.com or call (210) 487-7463 in San Antonio or (832) 919-7990 in Houston.

Related Linkswww.facebook.com/saspinewww.instagram.com/surgical.associates.in.spine

If you've been living with back pain, you're not alone. Here at SASpine, we have experienced spine specialists who are committed to improving your quality of life. (PRNewsfoto/SASpine)

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SOURCE SASpine

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SASpine to offer Stem Cell Therapy - Yahoo Finance

Spinal Cord Stem Cells Comments Off on SASpine to offer Stem Cell Therapy – Yahoo Finance | February 3rd, 2020

A patient who received the worlds first transplant of cardiac muscle cells using artificially derived stem cells known as iPS cells this month is in stable condition, an Osaka University team said Jan. 27.

After surgery, doctors closely monitored the patient, who had ischemic cardiomyopathy, a condition in which clotted arteries cause heart muscles to malfunction. But the patient has been moved toa general hospital ward, the team said.

Yoshiki Sawa, a professor of cardiovascular surgery at the university, who led the team that conducted the transplant, said the team aims to put the technique into practical use.

Sawa said the team hopestransplants of heart muscle tissues derived from induced pluripotent stem cellswill be used to save many patients who have heart conditions.

In the clinical trial, three sheets of heart muscle tissues made from iPS cells stocked at Kyoto Universitys Center for iPS Cell Research and Application were attached to affected parts of the patients heart. The iPS cells were created from tissues provided by a healthy donor.

The sheets were 4 to 5 centimeters in diameter and 0.1 millimeter thick.

The transplant's goal is to regenerate cardiac blood vessels using a substance secreted by the sheets of muscle cells. The sheets are degradable and disappear from the body several months after they secrete the substance, according to the team.

The university plans to perform similar transplants on nine other patients who have serious heart problems.

The Osaka University team had planned to conduct the clinical trial of the transplant earlier after the government approved the plan in May 2018.

But it was postponed due to damage from a powerful earthquake that hit Osaka Prefecture the following month that rendered its facility to cultivate cells unusable.

The trial is part of the process toward the future distribution of medical products using cells.

Osaka Universitys announcement of the successful transplant of tissues created from iPS cells marked the fourth such transplantation.

Including Osaka University's trial, Japanese surgeons have now successfully transplanted tissues created from iPS cells four times.

The world's first transplant of iPS-derived cells was conducted in 2014 whenthe Riken research institute transplanted retina cells for a patient with age-related macular degeneration.

In 2018, Kyoto University transplanted nerve cells for a Parkinson disease patient. Osaka University transplanted cornea cells into a patient with a disease of the cornea in 2019.

Patients who undergo transplants using iPS-derived cell must accept the risk that the cells may become cancerous.

The moreiPS-derived cells a patient receives, the higher their risk.

Hundreds of thousands of retina cells were used in the 2014 retina transplant. In the 2018 and 2019 transplants, the number of nerve and cornea cells used soared to between 5 million to 6 million.

Osaka University's latest transplant utilized roughly 100 milliontissues made from iPS cells.

Sawa acknowledged the transplanted heart muscle tissues could turn cancerous, but said the teamhas made great efforts to remove potentially cancerous cells.

Hideyuki Okano, professor of molecular neurobiology at Keio University, who is researching the application of iPS-derived nerve cells to treat patients with spinal cord damage, said the risk was worth it.

Okano said the Osaka University's transplant, using tissues made from iPS cells from a donor, could be more effective than the existing therapy, which uses the patients own muscle tissues.

I understand that the transplanted tissues might become cancerous or cause an erratic heart rhythm, but the transplantation of the iPS-derived heart muscle tissues can be more effective than muscle tissue sheets made from the patients leg, Okano said.

Keio University is also planning to conduct clinical research using iPS-derived cells to regenerate heart tissues.

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Patient in Japan 1st to have iPS cell heart muscle transplant : The Asahi Shimbun - Asahi Shimbun

Spinal Cord Stem Cells Comments Off on Patient in Japan 1st to have iPS cell heart muscle transplant : The Asahi Shimbun – Asahi Shimbun | February 3rd, 2020

Neuralstem (NASDAQ:CUR) and SpringWorks Therapeutics (NASDAQ:SWTX) are both small-cap medical companies, but which is the better investment? We will contrast the two companies based on the strength of their analyst recommendations, earnings, institutional ownership, profitability, valuation, dividends and risk.

Earnings & Valuation

This table compares Neuralstem and SpringWorks Therapeutics gross revenue, earnings per share and valuation.

SpringWorks Therapeutics has lower revenue, but higher earnings than Neuralstem.

Institutional and Insider Ownership

38.3% of Neuralstem shares are owned by institutional investors. Comparatively, 72.1% of SpringWorks Therapeutics shares are owned by institutional investors. 5.4% of Neuralstem shares are owned by insiders. Strong institutional ownership is an indication that hedge funds, endowments and large money managers believe a stock is poised for long-term growth.

Profitability

This table compares Neuralstem and SpringWorks Therapeutics net margins, return on equity and return on assets.

Analyst Ratings

This is a summary of current ratings and target prices for Neuralstem and SpringWorks Therapeutics, as reported by MarketBeat.

SpringWorks Therapeutics has a consensus price target of $35.50, suggesting a potential upside of 12.77%. Given SpringWorks Therapeutics higher possible upside, analysts plainly believe SpringWorks Therapeutics is more favorable than Neuralstem.

Summary

SpringWorks Therapeutics beats Neuralstem on 6 of the 8 factors compared between the two stocks.

Neuralstem Company Profile

Neuralstem, Inc., a clinical stage biopharmaceutical company, focuses on the research and development of nervous system therapies based on its proprietary human neuronal stem cells and small molecule compounds. The company's stem cell based technology enables the isolation and expansion of human neural stem cells from various areas of the developing human brain and spinal cord enabling the generation of physiologically relevant human neurons of various types. Its lead product candidate is NSI-189, a chemical entity, which has been completed Phase II clinical trial for the treatment of major depressive disorder, as well as is in preclinical study for the treatment-refractory depression, Angelman Syndrome, Alzheimer's disease, ischemic stroke, diabetic neuropathy, irradiation-induced cognitive deficit, and long-term potentiation enhancement. The company also develops NSI-566, which has completed Phase II clinical trial for treating amyotrophic lateral sclerosis disease; Phase II clinical trial for the treatment of chronic ischemic stroke; and Phase I clinical trials for the treatment of chronic spinal cord injury, as well as is in preclinical study for the traumatic brain injury. In addition, it develops NSI-532, which is in preclinical study for treatment of Alzheimer's disease; and NSI-777 that is in preclinical study for treatment of human demyelinating diseases. Neuralstem, Inc. was founded in 1996 and is headquartered in Germantown, Maryland.

SpringWorks Therapeutics Company Profile

SpringWorks Therapeutics, Inc., a clinical-stage biopharmaceutical company, acquires, develops, and commercializes medicines for underserved patient populations suffering from rare diseases and cancer. Its advanced product candidate is nirogacestat, an oral small molecule gamma secretase inhibitor that is in Phase 3 clinical trials for the treatment of desmoid tumors. The company is also developing mirdametinib, an oral small molecule MEK inhibitor that is in Phase 2b clinical trials for the treatment of neurofibromatosis type 1-associated plexiform neurofibromas; and Nirogacestat + belantamab mafodotin, which is in Phase 1b clinical trials for the treatment of relapsed or refractory multiple myeloma. In addition, it is developing Mirdametinib + lifirafenib, a combination therapy that is in Phase 1b clinical trials in patients with advanced or refractory solid tumors; and BGB-3245, an investigational oral selective small molecule inhibitor of specific BRAF driver mutations and genetic fusions, which is in preclinical studies in a range of tumor models with BRAF mutations or fusions. The company has collaborations with BeiGene, Ltd. and GlaxoSmithKline plc to develop combination approaches with nirogacestat and mirdametinib, as well as other standalone medicines. SpringWorks Therapeutics, Inc. was founded in 2017 and is headquartered in Stamford, Connecticut.

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Neuralstem (NASDAQ:CUR) & SpringWorks Therapeutics (NASDAQ:SWTX) Financial Review - Riverton Roll

Spinal Cord Stem Cells Comments Off on Neuralstem (NASDAQ:CUR) & SpringWorks Therapeutics (NASDAQ:SWTX) Financial Review – Riverton Roll | February 2nd, 2020

Scientists have developed the first treatment for pain using human stem cells, which provides lasting relief in mice in a single treatment, without side effects. If the treatment is successful in humans, it could be a major breakthrough in the development of new non-opioid, and non-addictive pain management, the researchers said.

"Nerve injury can lead to devastating neuropathic pain and for the majority of patients there are no effective therapies," said Greg Neely, an associate professor at the University of Sydney in Australia.

"This breakthrough means for some of these patients, we could make pain-killing transplants from their own cells, and the cells can then reverse the underlying cause of pain," Neely said in a statement.

The study, published in the journal Pain, used human induced pluripotent stem cells (iPSCs) derived from bone marrow to make pain-killing cells in the lab.

The iPSCs are cells which can develop into many different cell types in the body during early life, and growth.

The researchers then put the cells into the spinal cord of mice with serious neuropathic pain, caused by damage or disease affecting the nervous system.

"Remarkably, the stem-cell neurons promoted lasting pain relief without side effects," said study co-author Leslie Caron.

"It means transplant therapy could be an effective and long-lasting treatment for neuropathic pain. It is very exciting," Caron said.

Because the researchers can pick where to put the pain-killing neurons, they can target only the parts of the body that are in pain.

"This means our approach can have fewer side effects," said John Manion, a PhD student and lead author of research paper.

The stem cells used were derived from adult blood samples, the researchers noted.

Their next step will be to perform extensive safety tests in rodents and pigs.

They will then move to human patients suffering chronic pain within the next five years.

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First pain treatment using human stem cells developed - THE WEEK

Spinal Cord Stem Cells Comments Off on First pain treatment using human stem cells developed – THE WEEK | January 31st, 2020

As they do in many areas of medicine, stem cells hold great potential in treating injured spinal cords, but getting them where they need to go is a delicate undertaking. Scientists at the University of California San Diego (UCSD) are now reporting a breakthrough in this area, demonstrating a new injection technique in mice they say can deliver far larger doses of stem cells and avoid some of the dangers of current approaches.

The research focuses on the use of a type of stem cell known as a neural precursor cell, which can differentiate into different types of neural cells and hold great potential in repairing damaged spines. Currently, these are directly injected into the primary cord of nerve fibers called the spinal parenchyma.

As such, there is an inherent risk of (further) spinal tissue injury or intraparechymal bleeding, says Martin Marsala, professor in the Department of Anesthesiology at UCSD School of Medicine.

In experiments on rodents, Marsala and his team have demonstrated a safer and less invasive approach. The scientists instead injected the stem cells in between a protective layer around the spine called the pial membrane and the superficial layers of the spinal cord, a region known as the spinal subpial space.

This injection technique allows the delivery of high cell numbers from a single injection, says Marsala. Cells with proliferative properties, such as glial progenitors, then migrate into the spinal parenchyma and populate over time in multiple spinal segments as well as the brain stem. Injected cells acquire the functional properties consistent with surrounding host cells.

Following these promising early results, the scientists are hopeful that stem cells injected in this way could one day greatly accelerate healing and improve the strength of cell-replacement therapies for several spinal neurodegenerative disorders, including spinal traumatic injury, amyotrophic lateral sclerosis and multiple sclerosis. But first will come experiments on larger animal models closer to the human anatomy in size, which will help them fine tune their technique for the best results.

The goal is to define the optimal cell dosing and timing of cell delivery after spinal injury, which is associated with the best treatment effect, says Marsala.

The research was published in the journal Stem Cells Translational Medicine.

Source: University of California San Diego

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Spinal injury researchers find a sweet spot for stem cell injections - New Atlas

Spinal Cord Stem Cells Comments Off on Spinal injury researchers find a sweet spot for stem cell injections – New Atlas | January 31st, 2020

As amphibians go, axolotls are pretty cute. These salamanders sport a Mona Lisa half-smile and red, frilly gills that make them look dressed up for a party. You might not want them at your soiree, though: Theyre also cannibals. While rare now in the wild, axolotls used to hatch en masse, and it was a salamander-eat-salamander world. In such a harsh nursery, they evolved or maybe kept the ability to regrow severed limbs.

Their regenerative powers are just incredible, says Joshua Currie, a biologist at the Lunenfeld-Tanenbaum Research Institute in Toronto whos been studying salamander regeneration since 2011. If an axolotl loses a limb, the appendage will grow back, at just the right size and orientation. Within weeks, the seam between old and new disappears completely.

And its not just legs: Axolotls can regenerate ovary and lung tissue, even parts of the brain and spinal cord.

The salamanders exceptional comeback from injury has been known for more than a century, and scientists have unraveled some of its secrets. It seals the amputation site with a special type of skin called wound epithelium, then builds a bit of tissue called the blastema, from which sprouts the new body part. But until recently, the fine details of the cells and molecules needed to create a leg from scratch have remained elusive.

With the recentsequencingandassemblyof the axolotls giant genome, though, and thedevelopment of techniques to modify the creatures genes in the lab,regeneration researchers are now poised to discover those details. In so doing, theyll likely identify salamander tricks that could be useful in human medicine

Already, studies are illuminating the cells involved, and defining the chemical ingredients needed. Perhaps, several decades from now, people, too, might regrow organs or limbs. In the nearer future, the findings suggest possible treatments for ways to promote wound-healing and treat blindness.

The idea of human regeneration has evolved from an if to a when in recent decades, says David Gardiner, a developmental biologist at the University of California, Irvine. Everybody now is assuming that its just a matter of time, he says. But, of course, theres still much to do.

In a working limb, cells and tissues are like the instruments in an orchestra: Each contributes actions, like musical notes, to create a symphony. Amputation results in cacophony, but salamanders can rap the conductors baton and reset the remaining tissue back to order and all the way back to the symphonys first movement, when they first grew a limb in the embryo.

The basic steps are known: When a limb is removed, be it by hungry sibling or curious experimenter, within minutes the axolotls blood will clot. Within hours, skin cells divide and crawl to cover the wound with a wound epidermis.

Next, cells from nearby tissues migrate to the amputation site, forming a blob of living matter. This blob, the blastema, is where all the magic happens, said Jessica Whited, a regenerative biologist at Harvard University, in a presentation in California last year. It forms a structure much like the developing embryos limb bud, from which limbs grow.

This movie shows immune cells, labeled to glow green, moving within a regenerating axolotl fingertip. Scientists know that immune cells such as macrophages are essential for regeneration: When they are removed, the process is blocked.

Finally, cells in the blastema turn into all the tissues needed for the new limb and settle down in the right pattern, forming a tiny but perfect limb. This limb then grows to full size. When all is done, you cant even tell where the amputation occurred in the first place, Whited tellsKnowable Magazine.

Scientists know many of the molecular instruments, and some of the notes, involved in this regeneration symphony. But its taken a great deal of work.

As Currie started as a new postdoc with Elly Tanaka, a developmental biologist at the Research Institute of Molecular Pathology in Vienna, he recalls wondering, Where do the cells for regeneration come from? Consider cartilage. Does it arise from the same cells as it does in the developing embryo, called chondrocytes, that are left over in the limb stump? Or does it come from some other source?

To learn more, Currie figured out a way to watch individual cells under the microscope right as regeneration took place. First, he used a genetic trick to randomly tag the cells he was studying in a salamander with a rainbow of colors. Then, to keep things simple, he sliced off just a fingertip from his subjects. Next, he searched for cells that stuck out say, an orange cell that ended up surrounded by a sea of other cells colored green, yellow and so on. He tracked those standout cells, along with their color-matched descendants, over the weeks of limb regeneration. His observations, reported in the journalDevelopmental Cellin 2016,illuminated several secrets to the regeneration process.

Regenerative biologist Joshua Currie labeled the cells in axolotls with a rainbow of colors, so that he could follow their migration after he amputated the tip of the salamanders fingertips. In this image, three days after amputation, the skin (uncolored) has already covered the wound. (Credit: Josh Currie)

For one thing, cell travel is key. Cells are really extricating themselves from where they are and crawling to the amputation plane to form this blastema, Currie says. The distance cells will journey depends on the size of the injury. To make a new fingertip, the salamanders drew on cells within about 0.2 millimeters of the injury. But in other experiments where the salamanders had to replace a wrist and hand, cells came from as far as half a millimeter away.

More strikingly, Currie discovered that contributions to the blastema were not what hed initially expected, and varied from tissue to tissue. There were a lot of surprises, he says.

Chondrocytes, so important for making cartilage in embryos, didnt migrate to the blastema (earlier in 2016, Gardiner and colleaguesreported similar findings). And certain cells entering the blastema pericytes, cells that encircle blood vessels were able to make more of themselves, but nothing else.

The real virtuosos in regeneration were cells in skin called fibroblasts and periskeletal cells, which normally surround bone. They seemed to rewind their development so they could form all kinds of tissues in the new fingertip, morphing into new chondrocytes and other cell types, too.

To Curries surprise, these source cells didnt arrive all at once. Those first on the scene became chondrocytes. Latecomers turned into the soft connective tissues that surround the skeleton.

How do the cells do it? Currie, Tanaka and collaborators looked at connective tissues further, examining the genes turned on and off by individual cells in a regenerating limb. In a 2018Sciencepaper, the team reported thatcells reorganized their gene activation profileto one almost identical, Tanaka says, to those in the limb bud of a developing embryo.

Muscle, meanwhile, has its own variation on the regeneration theme. Mature muscle, in both salamanders and people, contains stem cells called satellite cells. These create new cells as muscles grow or require repair. In a 2017 study inPNAS, Tanaka and colleagues showed (by tracking satellite cells that were made to glow red) that most, if not all, ofmuscle in new limbs comes from satellite cells.

If Currie and Tanaka are investigating the instruments of the regeneration symphony, Catherine McCusker is decoding the melody they play, in the form of chemicals that push the process along. A regenerative biologist at the University of Massachusetts Boston, she recently published arecipe of sorts for creating an axolotl limb from a wound site. By replacing two of three key requirements with a chemical cocktail, McCusker and her colleagues could force salamanders to grow a new arm from a small wound on the side of a limb, giving them an extra arm.

Using what they know about regeneration, researchers at the University of Massachusetts tricked upper-arm tissue into growing an extra arm (green) atop the natural one (red). (Credit: Kaylee Wells/McCusker Lab)

The first requirement for limb regeneration is the presence of a wound, and formation of wound epithelium. But a second, scientists knew, was a nerve that can grow into the injured area. Either the nerve itself, or cells that it talks to, manufacture chemicals needed to make connective tissue become immature again and form a blastema. In their 2019 study inDevelopmental Biology, McCusker and colleagues guided byearlier work by a Japanese team used two growth factors, called BMP and FGF, to fulfill that step in salamanders lacking a nerve in the right place.

The third requirement was for fibroblasts from opposite sides of a wound to find and touch each other. In a hand amputation, for example, cells from the left and right sides of the wrist might meet to correctly pattern and orient the new hand. McCusckers chemical replacement for this requirement was retinoic acid, which the body makes from vitamin A. The chemical plays a role in setting up patterning in embryos and has long been known to pattern tissues during regeneration.

In their experiment, McCuskers team removed a small square of skin from the upper arm of 38 salamanders. Two days later, once the skin had healed over, the researchers made a tiny slit in the skin and slipped in a gelatin bead soaked in FGF and BMP. Thanks to that cocktail, in 25 animals the tissue created a blastema no nerve necessary.

About a week later, the group injected the animals with retinoic acid. In concert with other signals coming from the surrounding tissue, it acted as a pattern generator, and seven of the axolotls sprouted new arms out of the wound site.

The recipe is far from perfected: Some salamanders grew one new arm, some grew two, and some grew three, all out of the same wound spot. McCusker suspects that the gelatin bead got in the way of cells that control the limbs pattern. The key actions produced by the initial injury and wound epithelium also remain mysterious.

Its interesting that you can overcome some of these blocks with relatively few growth factors, comments Randal Voss, a biologist at the University of Kentucky in Lexington. We still dont completely know what happens in the very first moments.

If we did know those early steps, humans might be able to create the regeneration symphony. People already possess many of the cellular instruments, capable of playing the notes. We use essentially the same genes, in different ways, says Ken Poss, a regeneration biologist at the Duke University Medical Center in Durham who describednew advances in regeneration, thanks to genetic tools, in the 2017Annual Review of Genetics.

Regeneration may have been an ability we lost, rather than something salamanders gained. Way back in our evolutionary past, the common ancestors of people and salamanders could have been regenerators, since at least one distant relative of modern-day salamanders could do it. Paleontologists have discovered fossils of300-million-year-old amphibians with limb deformities typically created by imperfect regeneration.Other members of the animal kingdom, such as certain worms, fish and starfish, can also regenerate but its not clear if they use the same symphony score, Whited says.

These fossils suggest that amphibians calledMicromelerpetonwere regenerating limbs 300 million years ago. Thats because the fossils show deformities, such as fused bones, that usually occur when regrowth doesnt work quite right. (Credit: Nadia B Frbisch et al./Proceedings of the Royal Society B, 2014)

Somewhere in their genomes, all animals have the ability, says James Monaghan, a regeneration biologist at Northeastern University in Boston. After all, he points out, all animals grow body parts as embryos. And in fact, people arent entirely inept at regeneration. We can regrow fingertips, muscle, liver tissue and, to a certain extent, skin.

But for larger structures like limbs, our regeneration music falls apart. Human bodies take days to form skin over an injury, and without the crucial wound epithelium, our hopes for regeneration are dashed before it even starts. Instead, we scab and scar.

Its pretty far off in the future that we would be able to grow an entire limb, says McCusker. I hope Im wrong, but thats my feeling.

She thinks that other medical applications could come much sooner, though such as ways to help burn victims. When surgeons perform skin grafts, they frequently transfer the top layers of skin, or use lab-grown skin tissue. But its often an imperfect replacement for what was lost.

Thats because skin varies across the body; just compare the skin on your palm to that on your calf or armpit. The tissues that help skin to match its body position, giving it features like sweat glands and hair as appropriate, lie deeper than many grafts. The replacement skin, then, might not be just like the old skin. But if scientists could create skin with better positional information, they could make the transferred skin a better fit for its new location.

Monaghan, for his part, is thinking about regenerating retinas for people who have macular degeneration or eye trauma. Axolotls can regrow their retinas (though, surprisingly, their ability to regenerate the lens is limited to hatchlings). He is working with Northeastern University chemical engineer Rebecca Carrier, whos been developing materials for use in transplantations. Her collaborators are testing transplants in pigs and people, but find most of the transplanted cells are dying. Perhaps some additional material could create a pro-regeneration environment, and perhaps axolotls could suggest some ingredients.

Carrier and Monaghan experimented with the transplanted pig cells in lab dishes, and found they were more likely to survive and develop into retinal cells if grown together with axolotl retinas. The special ingredientseems to be a distinct set of chemicals that exist on axolotl, but not pig, retinas.Carrier hopes to use this information to create a chemical cocktail to help transplants succeed. Even partially restoring vision would be beneficial, Monaghan notes.

Thanks to genetic sequencing and modern molecular biology, researchers can continue to unlock the many remaining mysteries of regeneration: How does the wound epithelium create a regeneration-promoting environment? What determines which cells migrate into a blastema, and which stay put? How does the salamander manage to grow a new limb of exactly the right size, no larger, no smaller? These secrets and more remain hidden behind that Mona Lisa smile at least for now.

10.1146/knowable-012920-1

This article originally appeared in Knowable Magazine, an independent journalistic endeavor from Annual Reviews.

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What the Axolotl's Limb-Regenerating Capabilities Have to Teach Us - Discover Magazine

Spinal Cord Stem Cells Comments Off on What the Axolotl’s Limb-Regenerating Capabilities Have to Teach Us – Discover Magazine | January 31st, 2020

An international research team, led by physician-scientists at University of California San Diego School of Medicine, describe a new method for delivering neural precursor cells (NSCs) to spinal cord injuries in rats, reducing the risk of further injury and boosting the propagation of potentially reparative cells.NSCs hold great potential for treating a variety of neurodegenerative diseases and injuries to the spinal cord. The stem cells possess the ability to differentiate into multiple types of neural cell, depending upon their environment. As a result, there is great interest and much effort to use these cells to repair spinal cord injuries and effectively restore related functions.

But current spinal cell delivery techniques, said Martin Marsala, MD, professor in the Department of Anesthesiology at UC San Diego School of Medicine, involve direct needle injection into the spinal parenchyma the primary cord of nerve fibers running through the vertebral column. "As such, there is an inherent risk of (further) spinal tissue injury or intraparechymal bleeding," said Marsala.

The new technique is less invasive, depositing injected cells into the spinal subpial space a space between the pial membrane and the superficial layers of the spinal cord.

"This injection technique allows the delivery of high cell numbers from a single injection," said Marsala. "Cells with proliferative properties, such as glial progenitors, then migrate into the spinal parenchyma and populate over time in multiple spinal segments as well as the brain stem. Injected cells acquire the functional properties consistent with surrounding host cells."

Marsala, senior author Joseph Ciacci, MD, a neurosurgeon at UC San Diego Health, and colleagues suggest that subpially-injected cells are likely to accelerate and improve treatment potency in cell-replacement therapies for several spinal neurodegenerative disorders in which a broad repopulation by glial cells, such as oligodendrocytes or astrocytes, is desired.

"This may include spinal traumatic injury, amyotrophic lateral sclerosis and multiple sclerosis," said Ciacci.

The researchers plan to test the cell delivery system in larger preclinical animal models of spinal traumatic injury that more closely mimic human anatomy and size. "The goal is to define the optimal cell dosing and timing of cell delivery after spinal injury, which is associated with the best treatment effect," said Marsala.ReferenceMarsala et al. (2019) Spinal parenchymal occupation by neural stem cells after subpial delivery in adult immunodeficient rats. Stem Cells Translational Medicine. DOI: https://doi.org/10.1002/sctm.19-0156

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Injection Innovation May Improve Spinal Cord Repair Research - Technology Networks

Spinal Cord Stem Cells Comments Off on Injection Innovation May Improve Spinal Cord Repair Research – Technology Networks | January 30th, 2020

Spinal cord injury (SCI) is a common disease with high incidence, disability rate and treatment cost. microRNA (miR)-200a is reported to inhibit Keap1 to activate Nrf2 signaling. This study aimed to explore the effects of lentivirus-mediated miR-200a gene-modified bone marrow mesenchymal stem cells (BMSCs) transplantation on the repair of SCI in a rat model. BMSCs were isolated from the bone marrow of Sprague-Dawley rats. miR-200a targeting to Keap1 was identified by luciferase-reporter gene assay. The expressions of Keap1, Nrf2, NQO-1, HO-1 and GCLC were detected by Western blotting in SCI rats. The locomotor capacity of the rats was evaluated using the Basso, Beattie and Bresnahan scale. The levels of malondialdehyde (MDA) and activities of superoxide dismutase (SOD) and catalase (CAT) were measured. miR-200a inhibited Keap-1 3 UTR activity in BMSCs. Transplantation of BMSCs with overexpression of miR-200a or si-Keap1increased locomotor function recovery of rats after SCI, while decreased MDA level, increased SOD, CAT activities and Nrf2 expression together with its downstream HO-1, NQO1, GCLC protein expressions in SCI rat. These results indicated that overexpressed miR-200a in BMSCs promoted SCI repair, which may be through regulating anti-oxidative signaling pathway. 2020 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

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Upregulation of microRNA-200a in bone marrow mesenchymal stem cells enhances the repair of spinal cord injury in rats by reducing oxidative stress and...

Spinal Cord Stem Cells Comments Off on Upregulation of microRNA-200a in bone marrow mesenchymal stem cells enhances the repair of spinal cord injury in rats by reducing oxidative stress and… | January 30th, 2020

In the 1986 horror classic The Fly, a scientist played by Jeff Goldblum manages, quite unintentionally, to mix his biology with that of a housefly with gruesome results.

But the real-world mutant fruit flies that scientists used to understand body patterning are almost as bizarre: Flies with legs on their brows instead of antennae. Flies with extra chest sections, complete with duplicate wings. Flies missing big chunks of their heads.

These freaky flies have something in common: Theyre mixing up their head-to-tail body plans. And they earned three scientists the Nobel Prize in Physiology or Medicine in 1995.

Two of the scientists, Eric Wieschaus and Christiane Nsslein-Volhard, conducted a now-famous genetic screen of fruit fly embryos in 1979 and 1980 while working at the European Molecular Biology Laboratory in Heidelberg, Germany. By feeding parent flies a powerful mutagen, they created a horde of larvae with genetic mistakes, including ones that affected how the fly embryo arranges bits of tissue, from head to tail, in sections a process called segmentation. (The pair tell the tale of this landmark experiment in the 2016 Annual Review of Cell and Developmental Biology.)

The other Nobel laureate, Edward Lewis of Caltech, discovered key players, later named Hox genes, that tell these fruit fly segments and other body parts what tissues and structures they should become.

Fruit flies, it turns out, have their own segmentation path, different from ours: They make a big chunk of tissue and then slice it up, like one would a loaf of bread. In contrast, vertebrates (including humans) churn out segments one by one, like a string of sausages, as they build the tissue. But many of the genes involved Hox and others found later are the same.

A landmark genetics screen by two scientists unearthed mutants with segmentation defects in the fruit fly Drosophila. On the left is the outer layer, or cuticle, of a normal early larva. To the right are ones of various mutants, with clear abnormalities.

CREDIT: E. WIESCHAUS & C. NSSLEIN-VOLHARD / AR CELL AND DEVELOPMENTAL BIOLOGY 2016

These commonalities extend to the need for a sort of ruler that guides segmentation and Hox actions by helping cells identify their position in the body. That ruler takes the form of a two-way gradient. Cells closest to the head end make lots of a chemical called retinoic acid, and those at the tail end make two other compounds, called FGF and Wnt. These diffuse along the body, such that different spots contain different amounts of the chemicals. So, for example, a cell thats closer to the head than the tail will know its position because its bathed in plenty of retinoic acid, but not so much Wnt or FGF.

Vertebrate segments arise from tissue called the mesoderm. Sandwiched between the cells that will make skin and those that will make most internal organs, the mesoderm will yield tissues such as bone and muscle.

As the embryo grows, part of the mesoderm tissue near the head begins to make its segments in the form of beads of tissue called somites, one on each side of the future spinal cord. They are squeezed out of that mesoderm like toothpaste from a tube, says Robb Krumlauf, a developmental biologist at the Stowers Institute for Medical Research in Kansas City, Missouri. These will turn into vertebrae and skeletal muscles. (Other body parts will develop from cells outside of the segments.)

If the segmentation process goes wrong, vertebrae can take the wrong shape: half-vertebrae, fused vertebrae or wedge-shaped ones, for example. In people, this causes a type of scoliosis, and also may affect the kidneys, heart and other body parts.

How does the embryo make just the right number of segments, all the right size? In the 1970s, English researchers came up with a model they called clock and wavefront. The embryos clock would tick to indicate each time a segment should be produced. The wavefront would consist of a maturation process traveling from head to tail, and cells at the crest of that maturation wave would be ready to segment. Whenever the clock ticked, they would spit out a new segment.

The developing mammalian embryo produces two somites, one each side of the future spinal canal, every time an internal clock ticks. The process is guided by a protein called FGF that is made by the tail end of the embryo and diffuses along its length, forming a gradient. Somite production occurs at a spot (the wave front) where the concentration of FGF is at just the right level when the clock makes a tick. The process repeats itself over and over, gradually building up segments, from which vertebrae and skeletal muscle are made. Two other molecules, Wnt and retinoic acid, also form gradients, and with FGF these are key to telling tissues where they are along an embryos length.

At that time, scientists had no idea what molecules would control either clock or wavefront, or if the theory was even correct. The first hard evidence for a clock came from experiments with chicken eggs, published in 1997.

Developmental biologist Olivier Pourqui, now at Harvard Medical School, was studying the chick version of a gene called hairy that is involved in segmentation in fruit flies. He and his colleagues saw the hairy gene turn on in a cyclical manner: starting out at the tail, and then closer to the head, every 90 minutes. And every 90 minutes, the embryo made a new segment.

That study confirmed that a ticking clock did underlie segmentation, says Michalis Averof, a comparative developmental biologist at CNRS in Lyon, France. In 2012, he reported a similar oscillator in beetles.

Scientists still dont know what sets that clocks pace, but they now know that a variety of other proteins, including two of those ruler proteins, Wnt and FGF (and another called Notch), turn on genes like hairy. The other part of the system the wavefront of maturation is characterized by concentrations of FGF. Since FGF is made at the tail end, levels of the protein will be highest there and lowest at the head. Cells that have a low enough level of FGF when the clock ticks will form a segment.

Changing the speed of the clock can have profound effects on the body plan, as Pourqui found in a 2008 study on snakes. Snakes have hundreds of vertebrae, compared to the few dozen in other vertebrates like chickens, mice and humans. How did this come to be? Compared with that of a mouse, their clock is accelerated, Pourqui found. The faster it ticks, the more segments get made, creating the snakes long spine. He doesnt yet know why the snake clock ticks faster, though.

The bone-and-muscle segments, and the rest of the embryos developing tissues, need instructions so that the ones near the front make shoulders and arms, the ones at the back end make hips and legs, and so on. This process, too, depends on the ruler laid down by retinoic acid, Wnt and FGF. The position of cells with respect to the ruler tells them which Hox genes to activate. The Hox genes then turn on other genes, to make the right size and shape of vertebrae, or a tail, arm, liver, etc.

Its complicated: Mammals have 39 different Hox genes, activated in different combinations along the body and with different parts to play. For example, mice usually grow a defined series of vertebrae, including 13 thoracic segments with ribs and six lumbar segments without. But when scientists bred mice to lack the Hox10 gene, the creatures grew little ribs on the lumbar segments. In rare cases in people, mutations in Hox genes cause diverse effects such as club foot, hair loss and extra fingers and toes.

Lewis, who worked with Hox mutant flies in the 1970s, also discovered a remarkable pattern to the Hox genes. In DNA, they are lined up in the same order in which they are produced, from head to tail, in the embryo. Genes at one end of the line spring into action in response to retinoic acid, with that signal emanating from the head; the other end responds to Wnt and FGF, signals from the rear.

A collection of genes called HOX are activated in different parts of an animals body plan, telling cells and tissues what to become. In the DNA, the genes line up in the same order as they are used in a developing embryo. There are remarkable similarities between the HOX genes of disparate creatures, such as fruit flies, mice and humans. In mammals, the HOX genes diversified so that there are four sets (HOX A, B, C and D) to the flys single set. Duplications also led to an expanded number of HOX genes in each set.

Much remains unknown about how bodies are arranged how the same set of Hox genes creates such different body plans in different animals, for example, and how the pace of the segmentation clock sets just right to make a spine to fit a snake or a mouse or a person. Studying such things in people, of course, is difficult. So Pourqui and colleagues recently turned to human stem cells in a dish.

Using genetic trickery, they engineered the cells to flash yellow every time a certain clock gene turned on. Watching for the yellow glow, the researchers detected a clock that had five hours between each tick. Pourqui now aims to figure out just what controls that five-hour timing.

Its astounding, Krumlauf says, how similar the parts of the body-plan system are across such a wide variety of organisms. Each animal uses many of the same genetic tools, in different ways, to create its own unique shape.

In that respect, then, its not so surprising that Jeff Goldblums character melded so completely with a fly. Wnt, FGF, Hox genes its how we apply them that makes us the creatures we are.

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How do bodies position arms, legs, wings and organs? - Knowable Magazine

Spinal Cord Stem Cells Comments Off on How do bodies position arms, legs, wings and organs? – Knowable Magazine | January 30th, 2020

GIOSTAR/HEAMGEN has developed and secured patented technology to manufacture lifesaving mature red blood cells from stem cells. The red blood cells are made utilizing a bioreactor that permits the production of mature red blood cells, under strictly controlled conditions, for transfusion therapy and replaces the need for a human blood donor. GIOSTAR/HEAMGEN mature red blood cells are safe and not compromised by inadequate pathogen detection and inactivation of diseases such as hepatitis C, HIV, hepatitis B and syphilis. The red blood cells are O-Negative (Universal Donor) to eliminate incompatibility and allosensitization reactions.

ATLANTA (PRWEB) January 29, 2020

GIOSTAR/HEAMGEN has developed and secured patented technology to manufacture lifesaving mature red blood cells from stem cells. The red blood cells are made utilizing a bioreactor that permits the production of mature red blood cells, under strictly controlled conditions, for transfusion therapy and replaces the need for a human blood donor. GIOSTAR/HEAMGEN mature red blood cells are safe and not compromised by inadequate pathogen detection and inactivation of diseases such as hepatitis C, HIV, hepatitis B and syphilis. The red blood cells are O-Negative (Universal Donor) to eliminate incompatibility and allosensitization reactions. Trauma situations often do not allow for adequate blood typing due to time restrictions, so the GIOSTAR/HEAMGEN red blood cells address that need effectively.

"There are three main problems for blood transfusions," stated Dr. Anand Srivastava, Founder and Chairman of GIOSTAR. "First we have to match the blood type. Second, there's not enough blood available every single time. And third, when we transfer blood from one person to another person, there is always a chance of the transfer of disease."

Watch a feature interview with Dr. Anand Srivastava on The DM Zone with host Dianemarie Collins.

The World Health Organization (WHO) published the first detailed analysis on the global supply and demand for blood in October 2019 and found that 119 out of 195 countries do NOT have enough blood in their blood banks to meet hospital needs. In those nations, which include every country in central, eastern, and western sub-Saharan Africa, Oceania (not including Australasia), and south Asia are missing roughly 102,359,632 units of blood, according to World Health Organization (WHO) goals. While total blood supply around the world was estimated to be around 272 million units, in 2017, demand reached 303 million units. That means the world was lacking 30 million units of blood, and in the 119 countries with insufficient supply, that shortfall reached 100 million units.

The global market opportunity for GIOSTAR/HEAMGEN technology presents not only a profitable and scalable business opportunity but also a significant social and environmental impact. The global market is estimated to be at least $ 85 Billion/year.

GIOSTAR/HEAMGEN has identified early entry global markets to include Military, Trauma, Asia (replace Hepatitis C contaminated blood products), Africa (AIDS contaminated blood), Newborns, Thalassemia patients, Allosensitized sickle cell disease patients. South Sudan was found to have the lowest supply of blood, at 46 units per 100,000 people. In fact, the country's need for blood was deemed 75 times greater than its supply. In India, which had the largest absolute shortage, there was a shortfall of nearly 41 million units, with demand outstripping supply by over 400 percent. Strategic investments are needed in many low-income and middle-income countries to expand national transfusion services and blood management systems. Oncology is a major user of blood transfusion but if countries don't have the capacity to manage the bulk of oncology, it will limit complex surgery options.

GIOSTAR/HEAMGEN has acquired the exclusive license to the patent for the technique for stem cell proliferation from University of California San Diego (UCSD). The founding team of GIOSTAR/HEAMGEN is comprised of the scientists and clinicians who were involved in creating the Intellectual Property at UCSD and has already achieved PROOF OF CONCEPT - the optimized lab scale proliferation of mature red blood cells - at UCSD as part of their research.

GIOSTAR/HEAMGEN is currently looking for strategic partnerships (Contact Doug@DMProductionsLLC.com) to accelerate the development of donor-independent red blood cells manufacturing capabilities and advance the proof of concept work already done (patented) around the manufacture of safe, universal donor, human red blood cells. GIOSTAR/HEAMGEN will also develop a full automated proprietary bioreactor using robotic technology to produce abundant quantities of red blood cells with a goal for cost-effective commercialization of fresh, human, universal donor Red Blood Cells (RBCs).

ABOUT GIOSTAR

Dr. Anand Srivastava is a Chairman and Cofounder of California based Global Institute of Stem Cell Therapy and Research (GIOSTAR) headquartered in San Diego, California, (U.S.A.). The company was formed with the vision to provide stem cell based therapy to aid those suffering from degenerative or genetic diseases around the world such as Parkinson's, Alzheimer's, Autism, Diabetes, Heart Disease, Stroke, Spinal Cord Injuries, Paralysis, Blood Related Diseases, Cancer and Burns. GIOSTAR is a leader in developing most advance stem cell based technology, supported by leading scientists with the pioneering publications in the area of stem cell biology. Company's primary focus is to discover and develop a cure for human diseases with the state of the art unique stem cell based therapies and products. The Regenerative Medicine provides promise for treatments of diseases previously regarded as incurable.

GIOSTAR is world's leading Stem cell research company involved with stem cell research work for over a decade. It is headed by Dr Anand Srivastava, who is a pioneer and a world-renowned authority in the field of Stem Cell Biology, Cancer and Gene therapy. Several governments and organizations including USA, India, China, Turkey, Kuwait, Thailand, Philippines, Bahamas, Saudi Arabia and many others seek his advice and guidance on drafting their strategic and national policy formulations and program directions in the area of stem cell research, development and its regulations. Under his creative leadership, a group of esteemed scientists and clinicians have developed and established Stem Cell Therapy for various types of autoimmune diseases and blood disorders, which are being offered to patients in USA and soon it will be offered on a regular clinical basis to the people around the globe.

For the original version on PRWeb visit: https://www.prweb.com/releases/giostar_announces_medical_breakthrough_in_biotechnology_and_lifesciences_to_manufacture_abundant_safe_red_blood_cells_from_stem_cells/prweb16854975.htm

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GIOSTAR Announces Medical Breakthrough in Biotechnology and Lifesciences To Manufacture Abundant, Safe Red Blood Cells From Stem Cells - Benzinga

Spinal Cord Stem Cells Comments Off on GIOSTAR Announces Medical Breakthrough in Biotechnology and Lifesciences To Manufacture Abundant, Safe Red Blood Cells From Stem Cells – Benzinga | January 30th, 2020

CHICAGO - Brian Wallach wasn't supposed to live to see his younger daughter's first birthday.

Diagnosed with amyotrophic lateral sclerosis (ALS), a terminal disease with no cure, doctors told him in 2017 that he might have six months to live.

Today, he's focused on being there for his daughter's future firsts: kindergarten drop-off, middle school dance, wedding day.

More than two years after his diagnosis, he has been lucky, he said, to experience relatively limited progression of his disease. After some balance issues, the Kenilworth resident now uses a cane - or, as he is careful to specify, a "cool walking stick" - to get around.

When Wallach was diagnosed, neither he nor his wife, Sandra Abrevaya, knew much about ALS, a neurodegenerative disease that affects nerve cells in the brain and the spinal cord, eventually paralyzing even the body's ability to breathe.

In response to Wallach's diagnosis, the couple, both 39, launched I AM ALS in 2019. Former staffers in the Obama White House, they marshaled lessons learned while campaigning - gathering information, forming consensus, considering the impossible possible - to build a force to mobilize hope and change for those facing a disease they say can and should be cured.

Rays of hope are beginning to emerge through an innovative trial that received FDA approval last week to test several drugs at the same time, a bipartisan congressional caucus, doubled federal funding, and support from groups like the Chan Zuckerberg Initiative, which gave the couple's organization a $453,000 grant in September.

"Last year we made hope a word that was OK to use," Wallach said. "This year we have to make hope real."

Audaciousness is the only option, the couple says, in their race against the clock.

Wallach logged 120,000 miles in the air last year, including traveling to Washington, D.C., in April, where he testified before Congress and asked legislators to amp up funding.

"Last year, every time someone said, 'Do you want to speak to us,' I said, 'yes.' Every time someone said, 'There's a meeting,' I said, 'I'm going.'" he said. "Every time there was anything, I said, 'Great, I'm on the plane.'"

Until October, when Wallach fell while exiting a Lyft in Boston after swinging a heavy backpack onto his back. Thirteen staples in his head later, and after terrifying Abrevaya with a phone call, the two agreed he wouldn't travel alone anymore. He's maintaining momentum for the cause with more hours in his home office and fewer in airports.

In December, I AM ALS debuted billboards around Times Square as part of its #CuresForAll campaign aimed at informing the public about the impact a cure or better treatment for a neurodegenerative disease can have on other diseases such as multiple sclerosis, Alzheimer's and Parkinson's. ALS patients and their families from states including Michigan, Maine and Colorado were in New York for the launch.

The billboards noted the number of people lost to ALS each day - 16 - with photographs of those who died in 2019. Days earlier, Pete Frates, a founder of the viral fundraiser the Ice Bucket Challenge, which raised $115 million, had died. He was 34.

The campaign was also shared on social media. The posts expressed the suffering and loss nationwide: a mother wrote about her son who was diagnosed at 20 and died at 28; a son posted in honor of his dad; Colorado Rep. Jason Crow posted a message honoring his cousin.

It's time, the couple said, to switch ALS conversations from a diagnosis rooted in darkness to the faces of people bravely moving forward. They want to speed development of potential cures and give patients more access to experimental treatments.

That's not an unreasonable goal, said Sabrina Paganoni, a faculty member at The Sean M. Healey & AMG Center for ALS at Mass General in Boston, which plans to test at least five different medications for ALS at the same time, a first for the disease and something she said could be a huge turning point.

On Wednesday, the Healey Center announced it received FDA approval to move forward with testing the first three drugs: Zilucoplan, Verdiperstat and CNM-Au8. Similar to how cancer drugs are already tested, this gives patients access to more treatments and allows researchers to quickly collect data and accelerate the pace toward a cure.

"This is a very exciting time in the history of ALS," Paganoni said. "I think this is going to be the decade when ALS is changed from a rapidly fatal disease to a more chronic disease that we can manage."

For years, Steve Perrin, the chief executive officer at the ALS Therapy Development Institute, has monitored clinical trials for ALS. So far, he said, the two drugs approved by the FDA, Radicava and Rilutek, are "a very marginal slowing down of disease."

This year, he said the quality of drugs going into trials seems improved. He is excited about several trials, including one studying stem cells and another testing a drug to potentially slow progression in some patients.

"As a patient you want to see something measurable, and I don't mean measurable in days," he said. "If I'm a patient, I want to see something, and I want hope for myself and my family. I want something that is going to slow the disease down so I can watch my kids growing up, I can watch them graduate from college, I can watch them marry."

But that takes resources.

"We are in a time when we can reasonably say that there's going to be new treatments available," Paganoni said. "But we need more funding and support, so all of this can happen, and happen soon."

Nearly every moment feels like a push-pull for Wallach and Abrevaya.

Do they spend more precious minutes with their two daughters, ages 4 and 2, or do they spend time away, among strangers - on a plane, in a researcher's office, walking the halls of Congress - with the hope that those minutes will, someday, result in time banked to create more family memories.

"The hardest balance, if I'm honest, is, I love every minute I have with them," Wallach said about his daughters, "but I also feel this pressing sense of, I need to be working towards a goal of actually finding a cure."

"We're doing that so we have a shot at a real future together," Abrevaya said about their time spent traveling and advocating.

At home, when the family heads for the door, the toddlers reach for their father's shoes, and they get his walking stick.

"While that both fills your heart with joy and appreciation, it's also painful that your toddlers are being put in this position," Abrevaya said.

The parents guard normalcy. They take their daughters to swim at the neighborhood pool and on vacation with friends. Wallach wishes he could lift them above his head to touch the ceiling, like their uncle can. But he can lie on the floor and play with them; he can listen to them belt out songs on their purple karaoke machine.

They find ways to lighten a heavy subject. On New Year's Eve, the two danced in a video on the foundation's Instagram, singing into hairbrushes, and Wallach promised to get an "ALS: You Gone" tattoo if 20,000 people donated $10 to a Healey Center research fundraiser. It raised $40,000 in 24 hours, Wallach said. No matter the outcome, he plans to get the tattoo.

The couple, who both work full-time jobs - Abrevaya is the president of nonprofit Thrive, Wallach works at law firm Skadden, Arps, Slate, Meagher & Flom - want more research, to create a patient navigation system, and to gather signatures for a letter asking new FDA commissioner Stephen Hahn to speed ALS patients' access to possible treatments.

And they keep looking for light. But it takes work.

Changing life with ALS for Wallach, and for other patients and their families, requires bold action from people with the power to make change: politicians, researchers, philanthropists.

As they meet others with ALS, they welcome new friends and face the pain of losing some.

"It does make you uniquely urgent in what you do," Wallach said. "You push because you have to. You push because you know that the time that we have is precious, and that you want to see 20 years from now. And know that you can make that happen."

Wallach often shares moments about his ALS journey on Twitter with his 40,000 followers. Recently, he shared something he wasn't sure he should. It was a time he was unable to find light.

On a recent night, he woke up to pain he's had for the past few months, radiating from his right hip to his right calf.

He clutched a stuffed llama his daughter gave him. And he began to cry.

"I cried because of the pain. I cried because I couldn't be the father to my girls I dreamed of being," he wrote. "I cried because I couldn't be the husband to my wife I dream of being. Because I saw the future zooming ahead, and for a brief moment I wondered if I would be a part of it."

His wife heard him crying that night. She asked what was wrong. And he said maybe they would be better off if he left, living instead in an assisted living facility. Their daughters, he told her, could have a dad who could do everything he dreamed of doing.

She looked at him in the dark. "You are my light," she said. "You are their light. The only way you are leaving us is if you die in my arms, and we aren't going to let that happen for a long, long, long time."

Distributed by Tribune Content Agency, LLC.

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In a race against terminal illness, former Obama staffer with ALS and his wife find new hope a year later - PostBulletin.com

Spinal Cord Stem Cells Comments Off on In a race against terminal illness, former Obama staffer with ALS and his wife find new hope a year later – PostBulletin.com | January 27th, 2020

CHICAGO Brian Wallach wasnt supposed to live to see his younger daughters first birthday.

Diagnosed with amyotrophic lateral sclerosis (ALS), a terminal disease with no cure, doctors told him in 2017 that he might have six months to live.

Today, hes focused on being there for his daughters future firsts: kindergarten drop-off, middle school dance, wedding day.

More than two years after his diagnosis, he has been lucky, he said, to experience relatively limited progression of his disease. After some balance issues, the Kenilworth resident now uses a cane or, as he is careful to specify, a cool walking stick to get around.

When Wallach was diagnosed, neither he nor his wife, Sandra Abrevaya, knew much about ALS, a neurodegenerative disease that affects nerve cells in the brain and the spinal cord, eventually paralyzing even the bodys ability to breathe.

In response to Wallachs diagnosis, the couple, both 39, launched I AM ALS in 2019. Former staffers in the Obama White House, they marshaled lessons learned while campaigning gathering information, forming consensus, considering the impossible possible to build a force to mobilize hope and change for those facing a disease they say can and should be cured.

Rays of hope are beginning to emerge through an innovative trial that received FDA approval last week to test several drugs at the same time, a bipartisan congressional caucus, doubled federal funding, and support from groups like the Chan Zuckerberg Initiative, which gave the couples organization a $453,000 grant in September.

Last year we made hope a word that was OK to use, Wallach said. This year we have to make hope real.

Audaciousness is the only option, the couple says, in their race against the clock.

Wallach logged 120,000 miles in the air last year, including traveling to Washington, D.C., in April, where he testified before Congress and asked legislators to amp up funding.

Last year, every time someone said, Do you want to speak to us, I said, yes. Every time someone said, Theres a meeting, I said, Im going. he said. Every time there was anything, I said, Great, Im on the plane.

Until October, when Wallach fell while exiting a Lyft in Boston after swinging a heavy backpack onto his back. Thirteen staples in his head later, and after terrifying Abrevaya with a phone call, the two agreed he wouldnt travel alone anymore. Hes maintaining momentum for the cause with more hours in his home office and fewer in airports.

In December, I AM ALS debuted billboards around Times Square as part of its #CuresForAll campaign aimed at informing the public about the impact a cure or better treatment for a neurodegenerative disease can have on other diseases such as multiple sclerosis, Alzheimers and Parkinsons. ALS patients and their families from states including Michigan, Maine and Colorado were in New York for the launch.

The billboards noted the number of people lost to ALS each day 16 with photographs of those who died in 2019. Days earlier, Pete Frates, a founder of the viral fundraiser the Ice Bucket Challenge, which raised $115 million, had died. He was 34.

The campaign was also shared on social media. The posts expressed the suffering and loss nationwide: a mother wrote about her son who was diagnosed at 20 and died at 28; a son posted in honor of his dad; Colorado Rep. Jason Crow posted a message honoring his cousin.

Its time, the couple said, to switch ALS conversations from a diagnosis rooted in darkness to the faces of people bravely moving forward. They want to speed development of potential cures and give patients more access to experimental treatments.

Thats not an unreasonable goal, said Sabrina Paganoni, a faculty member at The Sean M. Healey & AMG Center for ALS at Mass General in Boston, which plans to test at least five different medications for ALS at the same time, a first for the disease and something she said could be a huge turning point.

On Wednesday, the Healey Center announced it received FDA approval to move forward with testing the first three drugs: Zilucoplan, Verdiperstat and CNM-Au8. Similar to how cancer drugs are already tested, this gives patients access to more treatments and allows researchers to quickly collect data and accelerate the pace toward a cure.

This is a very exciting time in the history of ALS, Paganoni said. I think this is going to be the decade when ALS is changed from a rapidly fatal disease to a more chronic disease that we can manage.

For years, Steve Perrin, the chief executive officer at the ALS Therapy Development Institute, has monitored clinical trials for ALS. So far, he said, the two drugs approved by the FDA, Radicava and Rilutek, are a very marginal slowing down of disease.

This year, he said the quality of drugs going into trials seems improved. He is excited about several trials, including one studying stem cells and another testing a drug to potentially slow progression in some patients.

As a patient you want to see something measurable, and I dont mean measurable in days, he said. If Im a patient, I want to see something, and I want hope for myself and my family. I want something that is going to slow the disease down so I can watch my kids growing up, I can watch them graduate from college, I can watch them marry.

But that takes resources.

We are in a time when we can reasonably say that theres going to be new treatments available, Paganoni said. But we need more funding and support, so all of this can happen, and happen soon.

Nearly every moment feels like a push-pull for Wallach and Abrevaya.

Do they spend more precious minutes with their two daughters, ages 4 and 2, or do they spend time away, among strangers on a plane, in a researchers office, walking the halls of Congress with the hope that those minutes will, someday, result in time banked to create more family memories.

The hardest balance, if Im honest, is, I love every minute I have with them, Wallach said about his daughters, but I also feel this pressing sense of, I need to be working towards a goal of actually finding a cure.

Were doing that so we have a shot at a real future together, Abrevaya said about their time spent traveling and advocating.

At home, when the family heads for the door, the toddlers reach for their fathers shoes, and they get his walking stick.

While that both fills your heart with joy and appreciation, its also painful that your toddlers are being put in this position, Abrevaya said.

The parents guard normalcy. They take their daughters to swim at the neighborhood pool and on vacation with friends. Wallach wishes he could lift them above his head to touch the ceiling, like their uncle can. But he can lie on the floor and play with them; he can listen to them belt out songs on their purple karaoke machine.

They find ways to lighten a heavy subject. On New Years Eve, the two danced in a video on the foundations Instagram, singing into hairbrushes, and Wallach promised to get an ALS: You Gone tattoo if 20,000 people donated $10 to a Healey Center research fundraiser. It raised $40,000 in 24 hours, Wallach said. No matter the outcome, he plans to get the tattoo.

The couple, who both work full-time jobs Abrevaya is the president of nonprofit Thrive, Wallach works at law firm Skadden, Arps, Slate, Meagher & Flom want more research, to create a patient navigation system, and to gather signatures for a letter asking new FDA commissioner Stephen Hahn to speed ALS patients access to possible treatments.

And they keep looking for light. But it takes work.

Changing life with ALS for Wallach, and for other patients and their families, requires bold action from people with the power to make change: politicians, researchers, philanthropists.

As they meet others with ALS, they welcome new friends and face the pain of losing some.

It does make you uniquely urgent in what you do, Wallach said. You push because you have to. You push because you know that the time that we have is precious, and that you want to see 20 years from now. And know that you can make that happen.

(EDITORS: STORY CAN END HERE)

Wallach often shares moments about his ALS journey on Twitter with his 40,000 followers. Recently, he shared something he wasnt sure he should. It was a time he was unable to find light.

On a recent night, he woke up to pain hes had for the past few months, radiating from his right hip to his right calf.

He clutched a stuffed llama his daughter gave him. And he began to cry.

I cried because of the pain. I cried because I couldnt be the father to my girls I dreamed of being, he wrote. I cried because I couldnt be the husband to my wife I dream of being. Because I saw the future zooming ahead, and for a brief moment I wondered if I would be a part of it.

His wife heard him crying that night. She asked what was wrong. And he said maybe they would be better off if he left, living instead in an assisted living facility. Their daughters, he told her, could have a dad who could do everything he dreamed of doing.

She looked at him in the dark. You are my light, she said. You are their light. The only way you are leaving us is if you die in my arms, and we arent going to let that happen for a long, long, long time.

Finally, he smiled.

2020 Chicago Tribune

Visit the Chicago Tribune at http://www.chicagotribune.com

Distributed by Tribune Content Agency, LLC.

PHOTOS (for help with images, contact 312-222-4194): ALS-BATTLE

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In a race against terminal illness, former Obama staffer with ALS and his wife find new hope a year later - Bryan-College Station Eagle

Spinal Cord Stem Cells Comments Off on In a race against terminal illness, former Obama staffer with ALS and his wife find new hope a year later – Bryan-College Station Eagle | January 26th, 2020

Researchers at Karolinska Institutet in Sweden have revealed a new principle of organisation which explains how locomotion is coordinated in vertebrates akin to an engine with three gears. The results are published in the scientific journal Neuron.

A remarkable feature of locomotion is its capacity for rapid starts and to change speed to match our intentions. However, there is still uncertainty as to how the rhythm-generating circuit - the locomotor engine - in the spinal cord is capable of instantaneously translating brain commands into rhythmic and appropriately paced locomotion.

Using zebrafish as a model organism, researchers at Karolinska Institutet reveal in detail a full reconstruction of the rhythm-generating engine driving locomotion in vertebrates.

"We have uncovered a novel principle of organisation that is crucial to perform an intuitively simple, yet poorly understood function: the initiation of locomotion and the changing of speed," says Abdel El Manira, Professor at the Department of Neuroscience at Karolinska Institutet, who led the study.

The researchers performed a comprehensive and quantitative mapping of connections (synapses) between neurons combined with behavioural analyses in zebrafish. The results revealed that the excitatory neurons in the spinal cord which drive locomotion form three recurrent, rhythm-generating circuit modules acting as gears which can be engaged at slow, intermediate or fast locomotor speeds. These circuits convert signals from the brain into coordinated locomotor movements, with a speed that is aligned to the initial intention.

"The insights gained in our study can be directly applicable to mammals, including humans, given that the organising principle of the brainstem and spinal circuits is shared across vertebrate species," says Abdel El Manira. "Understanding how circuits in the brainstem and spinal cord initiate movements and how speed is controlled will open up for new research avenues aimed at developing therapeutic strategies for human neurological disorders, including traumatic spinal cord injury, and motoneuron degenerative diseases such as amyotrophic lateral sclerosis (ALS)."

Reference: Song, J., Pallucchi, I., Ausborn, J., Ampatzis, K., Bertuzzi, M., Fontanel, P., Picton, L. D., & Manira, A. E. (2020). Multiple Rhythm-Generating Circuits Act in Tandem with Pacemaker Properties to Control the Start and Speed of Locomotion. Neuron, 0(0). https://doi.org/10.1016/j.neuron.2019.12.030

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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The Spinal Cord Organizes Locomotion Like a Three-gear Engine - Technology Networks

Spinal Cord Stem Cells Comments Off on The Spinal Cord Organizes Locomotion Like a Three-gear Engine – Technology Networks | January 23rd, 2020