Preclinical evaluation of FasT CAR-T cellsFasT CAR-T (F-CAR-T) proliferation in vitro

To characterize the in vitro proliferative capacity of F-CAR-T cells, F-CAR-T and C-CAR-T cells were manufactured in parallel (Supplementary Methods, and Fig. S1) using T-cells from 6 B-ALL patients. To investigate the ex vivo proliferation of F-CAR-T, frozen CD19 F-CAR-T and C-CAR-T cells from each patient were thawed and stimulated with irradiated CD19-expressing K562 cells. The number of CD19-targeting CAR-T cells was then determined during the course of cell expansion in vitro. As shown in Fig. 1A, upon CD19 antigen stimulation, F-CAR-T proliferation was much more robust compared to C-CAR-T proliferation. On day 17 post co-culture, F-CAR-T expanded 1205.61226.3 fold (MeanSD), while C-CAR-T expanded only 116.437.2 fold (MeanSD), (p=0.001). To characterize the mechanism underlying the superior proliferative ability of F-CAR-T, we purified CD19+ CAR-T cells from both F-CAR-T and C-CAR-T. The expression of genes involved in cell proliferation, cell cycle, and apoptosis was analyzed using Nanostring (detailed gene sets are in Table S2). Gene expression profiles showed higher F-CAR-T expression scores for genes associated with cell cycle regulation (F-CAR-T vs. C-CAR-T, p<0.01) and lower expression scores for apoptosis-related genes (F-CAR-T vs. C-CAR-T, p<0.05) in F-CAR-T cells (Fig. S2A).

A Ex vivo cell proliferation of F-CAR-T and C-CAR-T derived from B-ALL patients (n=6) (***P=0.001, F-CAR-T vs. C-CAR-T, d17, unpaired student two-tailed t-test). B Tscm, Tcm, and Tem were characterized by surface staining of CD45RO and CD62L and analyzed with flow cytometry (***P<0.001 comparing F-CAR-T and C-CAR-T). C T-cell exhaustion was characterized by PD-1, LAG3, and TIM-3 staining; Statistical analyses of the percentage of PD1+ LAG3+ Tim3+ (***P<0.001, comparing F-CAR-T and C-CAR-T), unpaired student two-tailed t-test). D RTCA assay was used to examine the specific killing of HeLa-CD19 cells. Growth of target HeLa-CD19 or HeLa cells were monitored dynamically. E CD19+ target Nalm6-Luc cells or F Raji-Luc cells were co-cultured with either F-CAR-T or C-CAR-T for 6h. Target cell killing efficacy was calculated by luciferase activity. NS, P>0.05 F-CAR-T vs. C-CAR-T (unpaired student t-test, two-tailed). F-CAR-T FasT CAR-T, C-CAR-T conventional CAR-T, Tcm (CD45RO+CD62L+) T central memory cells, Tem (CD45RO+CD62L) T effector memory cells, Tscm (CD45ROCD62L+) T stem cell memory, PD1 programmed cell death protein 1, TIM-3 T cell immunoglobulin and mucin domain containing-3, LAG3 lymphocyte-activation gene 3, RTCA real-time cell analyzer, E:T effector cells: target cells, NT normal T-cell.

Phenotypes of unstimulated F-CAR-T from three healthy donors were analyzed by flow cytometry. The CD45ROCD62L+ population was 45.7%2.2% which was comparable to the un-transduced T-cells (data not shown). Upon stimulation with CD19+ tumor cells for 9 days, C-CAR-T central memory cells (Tcm, CD45RO+CD62L+ and effector memory cells (Tem, CD45RO+CD62L) were 56.62%11.97% and 40.48%9.70%, respectively, among the C-CAR-T cells (Fig. 1B and Figs. S2B and S2). In contrast, Tcm cells (87.92%4.36%) was predominant in F-CAR-T, with only a small fraction of Tem (7.84%3.79%). In addition, F-CAR-T cells demonstrated more abundant T stem cell memory (Tscm) (3.841.22% vs 2.342.48%, p<0.05) than C-CAR-T cells. We also examined the exhaustion status of the stimulated CAR-T cells. A higher percentage of PD-1+LAG3+Tim3+T-cells were detected in the C-CAR-T (11.19%2.54%) compared to F-CAR-T (3.59%2.51%, p<0.001) (Fig. 1C). Together these data indicated that the F-CAR-T exhibited a younger phenotype and was less exhausted compared to C-CAR-T.

We used a real-time cell analyzer (RTCA) assay to measure the cytotoxicity of F-CAR-T and C-CAR-T against CD19+ cells in vitro. F-CAR-T and C-CAR-T killing of Hela-CD19 target cells were comparable using this assay (Fig. 1D). Similar levels of IFN- and IL-2 production were also observed (Fig. S2D). In a luciferase-based cytotoxicity assay, CD19+ B leukemia cell lines, Raji and Nalm6, were both effectively killed to similar or better levels at different E:T ratios (Fig. 1E, F).

To compare the in vivo cytotoxicity of F-CAR-T and C-CAR-T, severe immunodeficient NOG mice were engrafted with Raji-luciferase cells. One week after the tumor grafts were established, F-CAR-T and C-CAR-T were intravenously injected at various doses. The engrafted tumors progressed aggressively in control groups with either vehicle alone or control T-cells (Fig. 2A). In contrast, F-CAR-T or C-CAR-T treatment greatly suppressed tumor growth in a dose-dependent manner (Fig. 2A). In the high dose group (2106/mice), both F-CAR-T and C-CAR-T eliminated the tumor rapidly. However, in the low dose group (5105/mice), F-CAR-T showed more effective tumor-killing compared to C-CAR-T. On day 20, mice in the low dose F-CAR-T group became tumor-free, while C-CAR-T treated mice exhibited tumor relapse (Fig. 2A). We examined the CAR-T cell expansion in vivo after infusion. As shown in Fig. 2B, both F-CAR-T and C-CAR-T began to expand in the peripheral blood 7 days after infusion. C-CAR-T cell numbers reached their peak on day 14 and receded on day 21. In contrast, the F-CAR-T cell number peaked on day 21 and declined to a baseline level on day 28. F-CAR-T not only persisted longer but also underwent 26 folds greater expansion than C-CAR-T (Fig. 2B).

A Raji-Luc cell engraftment NOG mice were given high dose (2106/mice, n=3) and low dose (5105/mice, n=3) F-CAR-T/C-CAR-T along with control groups. Tumor growth was monitored with IVIS scan once every 3 days; B CAR-T expansion in peripheral blood of mice was analyzed by flow cytometry (n=6). ***P<0.001 for F-CAR-T HD vs. C-CAR-T HD; F-CAR-T LD vs. C-CAR-T LD; F-CAR-T HD vs. F-CAR-T LD; C-CAR-T HD vs. C-CAR-T LD (two-way ANOVA statistical analysis); C Schematic of the Nalm6 (1106) xenograft model, CAR-T (2106) infused 1 day after cyclophosphamide (20mg/kg) treatment. Bone marrow infiltration of F-CAR-T was analyzed 10 days after CAR-T infusion (n=3); D CD45+CD2 F-CAR-T vs. C-CAR-T in peripheral blood of mice were analyzed by flow cytometry; *P<0.05 (unpaired student two-tailed t-test). IVIS in vivo imaging system, PB peripheral blood, i.v. intravenous, HD high dose, LD low dose, Cy cyclophosphamide; *p<0.05; #: number.

We examined the BM infiltration of F-CAR-T cells after infusion into Nalm6-bearing mice (Fig. 2C). A larger population of CAR-T cells was observed 10 days after infusion in BM in F-CAR-T infused group than that in the C-CAR-T group (p<0.05) (Fig. 2D), suggesting F-CAR-T cells possessed a better BM homing capability than C-CAR-T.

The chemokine receptor CXCR4 is known to be critical for BM homing of T-cells [25, 26]. Indeed, a higher percentage of CXCR4+ T cells were detected in F-CAR-T than in the C-CAR-T. Interestingly, this phenotype was more pronounced for CD4+ T cells than CD8+ T cells (Fig. S3A). In a two-chamber system, more F-CAR-T cells could be detected in the lower chamber than their C-CAR-T counterparts (Fig. S3B).

Between Jan. 2019 and Oct. 2019, 25 pediatric and adult patients with CD19+R/R B-ALL were enrolled onto our phase 1 trial, including two patients who had relapsed following a prior allo-HSCT. Patient characteristics are detailed in Table 1. The median age of patients was 20 (range: 344) years old. Twenty patients were >14 years old, and five were 14 years old. The median percentage of pre-treatment BM blasts was 9.05% (range: 0.1982.9%). As our pre-clinical studies demonstrated that F-CAR-T cells had a superior expansion capability as compared to C-CAR-T, we infused a relatively low doses of F-CAR-T cells, ranging from 104105 cells/kg: 3.0104 cells/kg (n=2), 6.5 (5.867.43)104 cells/kg (n=9), 1.01 (1.01.16)105 cells/kg (n=12), 1.52(1.471.56)105 cells/kg (n=2), (Fig. S4). The median time from apheresis to the infusion of CD19+F-CAR-T cells was 14 days (range: 1220). Although the manufacturing time of F-CAR-T was next day, the quality control time and detailed final product releases including sterility testing require a minimum of 710 days to complete. In addition, transportation of cell products requires approximately two days. Of the 25 patients who received CD19 F-CAR-T infusion, 22 (88%) received bridging chemotherapy between apheresis and lymphodepleting chemotherapy to control rapid disease progression (Table S3).

F-CAR-T cells were manufactured successfully for all patients. The mean transduction efficiency of F-CAR-T was 35.4% (range: 13.170.3%) (Fig. S5A). Both CD4+/CAR+ (mean, 49.6%; range: 13.673.2%) and CD8+/CAR+ (mean, 41.5%; range: 20.677.7%) subsets were present in the CD3+CAR+ T cell subsets of all products. The mean proportion of Tscm, Tem, and Tcm cells in the CD3+CAR+ T cell subsets of all products was 23.3% (range: 3.5545.3%), 33.2% (range: 17.267.9%), and 36.1% (range: 20.758.1%), respectively (Fig. S5B). F-CAR-T products exerted significant IFN- release and cytotoxic effects against the CD19+ cell line HELA-CD19 (Fig. S5, C, D).

All 25 infused patients experienced adverse events (AEs) of any grade, with 25 (100%) experiencing grade 3 or higher adverse events. No grade 5 events related to F-CAR-T treatment were observed (Table 2).

CRS occurred in 24 (96%) patients with 18 (72%) grade 12 CRS,6 (24%) of grade 3, and no grade 4 or higher CRS (Fig. S6). In the >14 years old group, 16/20 (80%) patients developed mild CRS, and only 2/20 (10%) developed grade 3 CRS. For 14 years old patients, 2/5 (40%) had mild CRS, yet 3/5 (60%) experienced grade 3 CRS (Table S4). ICANS was observed in 7 (28%) patients, with 2 (8%) grade 3 ICANS occurring in patients >14 years old and 5 (20%) grade 4 ICANS all occurring in patients 14 years old. No grade 5 ICANS was developed (Fig. S7 and Table S4). The most frequent presentation of CRS was fever, particularly a high fever of >39C. The first onset of CRS symptoms occurred between day 3 and 8 post-CAR-T infusion with a median onset at day 4 (range: 110 days). The most common symptoms of ICANS were seizure (5/7) and depressed consciousness (5/7). The median time to ICANS onset from CAR-T cell infusion was 7 days (range: 58), and the median time to resolution was 2 days (Fig. S7). All CRS and ICANS events were managed including early intervention when fever of 39C persisted for 24h. Sixteen (64%) patients received tocilizumab with a median total dose of 160mg (range: 160320mg). Twenty-one (84%) patients received corticosteroids including dexamethasone (median total dose, 43mg; range: 4127mg) and or methylprednisolone (median total dose, 190mg; range: 401070mg). The vast majority of these patients discontinued corticosteroids within 2 weeks. The change in IL-6, IFN-, IL-10, and GM-CSF levels after infusion are selectively shown in Fig. S8. The peak levels of these four cytokines were observed between day 710. Among all 21 cytokines examined, only post-infusion IL-6 levels were associated with moderate to severe CRS and/or ICANS (Figs. S9 and S10).

Superior in vivo proliferation and persistence of F-CAR-T compared to C-CAR-T cells were observed regardless of dose levels. The median peak level was reached on day 10 (range: 714 days) with 1.9105 transgene copies/g of genomic DNA (range: 0.225.2105 transgene copies/g of genomic DNA) by qPCR and 83 F-CAR-T cells per l blood (range: 42102 F-CAR-T cells per l blood) by FCM (Fig. 3A, B). No significant differences were observed among the different dose groups in the mean F-CAR-T copies peak (Fig. 3C). Importantly, there was no significant difference in the mean F-CAR-T copies peak between patients who received corticosteroids compared to those who did not (Fig. 3D).

A F-CAR-T cells in peripheral blood by qPCR. Purple, dose level 1; black, dose level 2; blue, dose level 3; red, dose level 4; B F-CAR-T cells in peripheral blood by flow cytometry. Purple, dose level 1; black, dose level 2; blue, dose level 3; red, dose level 4; C Comparison of the mean peak copy number of F-CAR-T cells in peripheral blood at each dose level. Statistical significance was determined by the MannWhitney test. D Comparison of the mean peak copy number of F-CAR-T cells in peripheral blood with or without steroids. Statistical significance was determined by the MannWhitney test.

Fourteen days after F-CAR-T cell infusion, all patients achieved morphologic CR including 2/25 with CR and 23/25 CR with incomplete hematologic recovery (CRi), which further improved to 11/25 CR and 14/25 CRi 28 days post F-CAR-T (Table 1 and Fig. 4). More importantly, 23/25 (92%) had the minimal residual disease (MRD)-negative remission on day 14 and day 28 after F-CAR-T treatment. Patients achieving remission through CAR-T were given the option to proceed to allo-HSCT. With a median time of 54 days (range: 4581 days) post F-CAR-T infusion, 20 of 23 patients with MRD-negative status decided to pursue consolidative allo-HSCT including one patient who received a 2nd transplant. As of 18 October 2021, with a median follow-up duration of 693 days (range: 84973 days) among the 20 patients who had received allo-HSCT, one patient relapsed on day 172 and died 3 months after relapse, and four patients died from transplant-related mortality (TRM) including infection (n=3) and chronic GVHD (n=1) on day 84, day 215, day 220, and day 312, respectively. The other 15 patients remained in MRD-negative CR with a median remission duration of 734 days (range: 208973) except for one who became MRD-positive on day 294 with CD19+ disease. Among the other three patients (F05, F06, F16), one remained in MRD-negative CR on day 304, one remained in MRD-negative CR until day 303, received allo-HSCT but died from an infection on day 505, and one was lost to follow-up after day 114. Two patients who had MRD-positive CR after infusion withdrew from the study on day 42 and day 44, respectively, to seek other studies.

Clinical outcomes and consolidative allo-HSCT for the 25 patients who were treated with F-CAR-T therapy are shown. On day 28, 23/25 patients achieved MRD-negative CR/CRi. With a median time of 54 days (range: 4581) post F-CAR-T infusion, 20 of 23 patients with MRD-negative status received consolidative allo-HSCT. Among the 20 patients, 1 patient (F23) relapsed on day 172 and died 3 months after relapse. Four patients (F04, F09, F11, F12) died from transplant-related mortality (TRM) including infection (n=3) and chronic GVHD (n=1) on day 84, day 215, day 220, and day 312, respectively. The remaining 15 patients were in MRD-negative CR except for one (F18) who became MRD-positive on day 294. Among the other 3 patients (F05, F06, F16), 1 remained MRD-negative CR on day 304, 1 remained in MRD-negative CR until day 303, received allo-HSCT, and subsequently died from an infection on day 505. One patient was lost to follow-up after day 114. MRD minimal residual disease, CR complete remission, Allo-HSCT allogeneic hematopoietic stem cell transplantation.

F-CAR-T/T ratio in cerebrospinal fluid (CSF) was evaluated by FCM in 13/25 patients with available samples (Table S5). Between days 10 and 32, 9 patients were found to have considerable F-CAR-T penetration in their CSF, ranging from 40.65 to 79.2%, including 4 who developed severe ICANS. Among the other 4 patients, F-CAR-T cell abundance in the CSF ranged from 1.29% to 3.57%, and none experienced severe ICANS. Patients with higher levels of CAR-T in PB on day 10 consistently had higher levels of CAR-T in CSF with the exception of patient F15. Notably, CAR-T cells were still detectable in the CSF on day 101 with a 2.36% CAR-T/T ratio in patient F06, who also had undetectable circulating CAR-T cells at the same time.

In addition, concentrations of seven cytokines (IL-1b, IL-6, IL-10, IFN-, TNF-, MCP-1, and GM-CSF) in CSF samples from the above 10 of 13 patients were measured. Specifically, IL-1b was not detected in any of the 10 patients, and only one patient had detectable GM-CSF. For the other five cytokines, patients with severe ICANS had higher IL-6 levels in contrast to patients without severe ICANS, and the difference between the median level of IL-6 among these two groups of patients was statistically significant (Fig. S11). We did not observe significant differences among the other 4 cytokines between the two groups of patients. No clear relation between the CSF cytokine levels and the F-CAR-T/T % was observed.

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Next-day manufacture of a novel anti-CD19 CAR-T therapy for B-cell acute lymphoblastic leukemia: first-in-human clinical study | Blood Cancer Journal...

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REDWOOD CITY, Calif., June 07, 2022 (GLOBE NEWSWIRE) -- Jasper Therapeutics, Inc. ( JSPR), a biotechnology company focused on enabling cures with stem cell therapies, today announced that the Company is participating in the William Blair 42nd Annual Growth Stock Conference, to be held in Chicago from June 6-9, 2022.

Ronald Martell, Jaspers Chief Executive Officer, is scheduled to present on Thursday, June 9th at 8:00AM CT, with a breakout session to follow at 8:40AM CT. A live webcast of the presentation will be available at https://wsw.com/webcast/blair66/jasp/1933236 and at the Companys Investor Events webpage.

About Jasper TherapeuticsJasper Therapeutics, Inc. is a biotechnology company focused on the development of novel curative therapies based on the biology of the hematopoietic stem cell. The company is advancing two potentially groundbreaking programs. JSP191, an anti-CD117 monoclonal antibody, is in clinical development as a conditioning agent that clears hematopoietic stem cells from bone marrow in patients undergoing hematopoietic cell transplantation. It is designed to enable safer and more effective, and potentially curative, allogeneic hematopoietic cell transplants and gene therapies. A clinical study of JSP191 as a novel, disease-modifying, therapeutic for patients with lower risk MDS is also planned to begin in 2022. In parallel, Jasper Therapeutics, Inc. is advancing its preclinical mRNA hematopoietic stem cell grafts platform, which is designed to overcome key limitations of allogeneic and autologous gene-edited stem cell grafts. Both innovative programs have the potential to transform the field and expand hematopoietic stem cell therapy cures to a greater number of patients with life-threatening cancers, genetic diseases and autoimmune diseases than is possible today. For more information, please visit us at jaspertherapeutics.com.

Forward-Looking StatementsCertain statements included in this press release that are not historical facts are forward-looking statements for purposes of the safe harbor provisions under the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements are sometimes accompanied by words such as believe, may, will, estimate, continue, anticipate, intend, expect, should, would, plan, predict, potential, seem, seek, future, outlook and similar expressions that predict or indicate future events or trends or that are not statements of historical matters. These forward-looking statements include, but are not limited to, statements regarding the potential of the Companys JSP191 and mRNA engineered stem cell graft programs. These statements are based on various assumptions, whether or not identified in this press release, and on the current expectations of Jasper and are not predictions of actual performance. These forward-looking statements are provided for illustrative purposes only and are not intended to serve as, and must not be relied on by an investor as, a guarantee, an assurance, a prediction or a definitive statement of fact or probability. Actual events and circumstances are difficult or impossible to predict and will differ from assumptions. Many actual events and circumstances are beyond the control of Jasper. These forward-looking statements are subject to a number of risks and uncertainties, including general economic, political and business conditions; the risk that the potential product candidates that Jasper develops may not progress through clinical development or receive required regulatory approvals within expected timelines or at all; risks relating to uncertainty regarding the regulatory pathway for Jaspers product candidates; the risk that prior study results may not be replicated; the risk that clinical trials may not confirm any safety, potency or other product characteristics described or assumed in this press release; the risk that Jasper will be unable to successfully market or gain market acceptance of its product candidates; the risk that Jaspers product candidates may not be beneficial to patients or successfully commercialized; patients willingness to try new therapies and the willingness of physicians to prescribe these therapies; the effects of competition on Jaspers business; the risk that third parties on which Jasper depends for laboratory, clinical development, manufacturing and other critical services will fail to perform satisfactorily; the risk that Jaspers business, operations, clinical development plans and timelines, and supply chain could be adversely affected by the effects of health epidemics, including the ongoing COVID-19 pandemic; the risk that Jasper will be unable to obtain and maintain sufficient intellectual property protection for its investigational products or will infringe the intellectual property protection of others; and other risks and uncertainties indicated from time to time in Jaspers filings with the SEC. If any of these risks materialize or Jaspers assumptions prove incorrect, actual results could differ materially from the results implied by these forward-looking statements. While Jasper may elect to update these forward-looking statements at some point in the future, Jasper specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing Jaspers assessments of any date subsequent to the date of this press release. Accordingly, undue reliance should not be placed upon the forward-looking statements.

Contacts:

John Mullaly (investors)LifeSci Advisors617-429-3548[emailprotected]

Jeet Mahal (investors)Jasper Therapeutics650-549-1403[emailprotected]

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Jasper Therapeutics to Participate in the William Blair 42nd Annual Growth Stock Conference - GuruFocus.com

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The very thought of getting someone elses poop transfused in your body may make you cringe but stool transplant has not only helped patients with gastrointestinal tract issues, it has also saved those who have had bone marrow transplants.

At Deenanath Mangeshkar Hospitals Centre of Excellence in Infectious Diseases and Department of Haematology, Pune, seven of the 11 patients of bone marrow transplants developed Clostridium difficile infection. They were treated with faecal microbial transplant (FMT), also referred to as stool transplant, over the past year.

Research worldwide has shown that a faecal transplant can restore healthy bacteria in the lower intestine which can help control Clostridium difficile or C. diff. According to the Johns Hopkins University School of Medicine, FMT can be more effective than antibiotics for keeping C. diff in check in some cases.

Since C. diff infection can recur and cause colitis (inflammation in the colon), FMT restores good and healthy bacteria, said Dr Parikshit Prayag, infectious disease consultant and in-charge of the Centre of Excellence in Infectious Diseases at Deenanath Mangeshkar hospital.

Dr Sameer Melinkeri, head of the department of haemotology at the hospital, said C. diff infection-related diarrhoea can occur in a normal setting in which antibiotics can be used for treatment. However, antibiotic treatment for recurrent infections can involve one or more courses of medication and their effectiveness comes down with each subsequent bout. FMT can arrest such infections post bone marrow transplant as it can be life-threatening, he added.

FMT is also done for certain disease conditions like Graft vs host disease (GvHD). Most people who undergo a bone marrow transplant suffer from blood cancer. Graft vs host disease can occur at any time after an allogeneic transplant where the donated bone marrow or peripheral stem cells can attack the recipients body. It can develop in the GI tract, skin or liver, Dr Prayag said.

Latest research published in the Journal of International Medical Research and others has shown how FMT is a promising treatment for patients with steroid-resistant GvHD. We have seen clinically relevant results in six of our patients, Dr Prayag said.

So, who can be donors? They are selected based on certain parameters. They should not be immune-compromised or have taken antibiotics over the past six months, says Dr Sampada Patwardhan, head of the department of microbiology at the hospital. Donor screening has to be done carefully. We need to rule out infections, she said.

Procedures on the transplant delivery methods may vary like colonoscopy and use of nasojejunal tube. The recovery may take a week or more and in most cases there are at least two weekly installations of the stool (in liquid form).

Very few centres conduct FMT and among them, the centre at Deenanath Hospital actively treats cases involving bone marrow transplants. At a recent virtual meeting of the International Society of Blood Transfusion, Dr Prayag made a strong case for encouraging stool transplants. The condition of C. diff is also underdiagnosed in the country as there isnt adequate infrastructure to correctly detect the problem, he pointed out.

In fact, FMT is being touted as a treatment option for many gut health issues. In an opinion article published on June 30 in the journal Trends in Molecular Medicine, a team from Harvard Medical School and Brigham and Womens Hospital (BWH) proposes that individuals bank samples of their own gut microbiota when they are young and healthy for potential use later in life in an autologous FMT.

A report in Science Daily quotes corresponding author Yang-Yu Liu, an associate professor of medicine at Harvard and an associate scientist in the Channing Division of Network Medicine at BWH, as saying, The idea of rewilding the human microbiome has taken off in recent years and has been hotly debated from medical, ethical and evolutionary perspectives. It is still unknown if people in industrialized societies can gain some health benefit by restoring their microbiome to an ancestral state. In this paper, we proposed a way to rejuvenate the human gut microbiome.

The report also listed OpenBiome, a non-profit stool bank based in Somerville, Massachusetts, as the first stool bank to offer an option for individuals to bank their own stool for future treatment of C. diff infection. Yang and his colleagues are now looking at if this treatment can be used for other diseases.

Conceptually, the idea of stool banking for autologous FMT is similar to when parents bank their babys cord blood for possible future use. However, there is greater potential for stool banking, and we anticipate that the chance of using stool samples is much higher than for cord blood. But there are many practical issues to implementing this idea, Yang is quoted as saying, hinting at optimal storage and cryopreservation issues.

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Cutting Edge: Poop therapy can save your gut, and your life - The Indian Express

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Ulcerative colitis, or UC, is a form of inflammatory bowel disease characterized by chronic and relapsing large intestine inflammation. Genetics account for only a minority of UC cases; hence, to develop treatments, researchers need to understand better the environmental contributions to this condition.

Gut microbes are in perpetual contact with the gastrointestinal tract, so they comprise important but poorly defined environmental variables contributing to UC development. Many studies have reported changes in gut microbiome composition in patients with UC compared to healthy individuals. While that suggests a potential role for gut microbes in UC pathogenesis, researchers have yet to pinpoint the causative microbes and associated bacterial proteins.

Dennis Wolans lab at Scripps Research is interested in identifying small-molecule activators and inhibiting bacterial enzymes involved in proliferation of human disease. Wolan said he was curious about what bacterial enzymes of the microbiome contribute to UC development.

Many publications have focused on the role of the microbiome in both health and disease states, he said. Most of these were focused on the taxonomical and phylogenic differences in the microbiome. But what about the associated bacterial proteins? What proteins are these gut bacteria making in disease conditions, and how are these interacting with the human body?

One protein of interest was serine proteases, a type of proteolytic enzyme that cleaves peptides at the serine amino acid. Researchers long have recognized that they coordinate many physiological processes and play key roles in regulating the inflammatory response. Previous studies have suggested increased proteolytic activity in microbial samples harvested from people with inflammatory disorders such as UC and Crohns disease.

Peter ThuyBuon, a graduate student and later a postdoc in the Wolan lab, led a project to study differential protein expression in healthy and UC fecal samples. He and the team described the project in a recent paper in the journal Molecular & Cellular Proteomics. In addition to standard mass spectrometry, ThuyBuon used a small molecular approach called affinity-based proteomic profiling to target and enrich for different types of proteases in the fecal samples.

We showed that there were 176 discrete host and microbial protein groups differentially enriched between healthy and UC patients, Wolan said. Furthermore, further enrichment of these proteins showed significantly higher levels of serine proteases in UC patients.

This finding has inspired exciting future research questions. For example, are elevated serine proteases the driver of UC or merely the effect of UC disease progression?

There is a lot of exciting work to be done using these findings, Wolan said. Future molecular studies should focus on how serine proteases might be contributing to UC and whether their levels can be manipulated to modify disease progression.

Functional proteomics has shown the potential role of serine proteases in UC. Future steps will include drug discovery and design of small-molecule regulators of bacterial enzymes.

Wolan said, Ultimately, the moderation of microbiome distribution in UC via external small-molecule intervention can serve as a foundation for UC prevention and treatment.

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Proteases implicated in ulcerative colitis - ASBMB Today

Bone Marrow Stem Cells Comments Off on Proteases implicated in ulcerative colitis – ASBMB Today | July 8th, 2022

Clusters of the earliest hematopoietic cells being born in the walls of the umbilical artery of a mouse embryo. The cells colored in red represent embryonic multipotent progenitor cells (eMPPs). Credit: Sachin H. Patel/Boston Childrens Hospital

Barcoding studies discovered two independent sources for blood cells in mice. If confirmed in humans, our understanding of blood cancers, bone marrow transplants, and the aging immune system will change.

The origins of our blood may not be quite what we thought. Using cellular barcoding in mice, groundbreaking research finds that blood cells originate not from one type of mother cell, but two, with potential implications for blood cancers, bone marrow transplant, and immunology. Fernando Camargo, PhD, of the Stem Cell Program at Boston Childrens Hospital led the study, published in the journal Nature on June 15, 2022.

Historically, people have believed that most of our blood comes from a very small number of cells that eventually become blood stem cells, also known as hematopoietic stem cells, says Camargo, who is also a member of the Harvard Stem Cell Institute and a professor at Harvard University. We were surprised to find another group of progenitor cells that do not come from stem cells. They make most of the blood in fetal life until young adulthood, and then gradually start decreasing.

The researchers are now following up to see if the findings also apply to humans. If so, these cells, known as embryonic multipotent progenitor cells (eMPPs), could potentially inform new treatments for boosting aging peoples immune systems. They could also shed new light on blood cancers, especially those in children, and help make bone marrow transplants more effective.

Camargos team applied a barcoding technique they developed several years ago. Using either an enzyme known as transposase or CRISPR gene editing, they inserted unique genetic sequences into embryonic mouse cells in such a way that all the cells descended from them also carried those sequences. This enabled the team to track the emergence of all the different types of blood cells and where they came from, all the way to adulthood.

Previously, people didnt have these tools, says Camargo. Also, the idea that stem cells give rise to all the blood cells was so embedded in the field that no one attempted to question it. By tracking what happened in mice over time, we were able to see new biology.

Through barcoding, the researchers found that eMPPs, as compared with blood stem cells, are a more abundant source of most lymphoid cells important to the immune responses, such as B cells and T cells. Camargo believes the decrease in eMPPs that they observed with age may explain why peoples immunity weakens as they get older.

Were now trying to understand why these cells peter out in middle age, which could potentially allow us to manipulate them with the goal of rejuvenating the immune system, says Camargo.

In theory, there could be two approaches: extending the life of eMPP cells, perhaps through growth factors or immune signaling molecules, or treating blood stem cells with gene therapy or other approaches to make them more like eMPPs.

Camargo is also excited about the potential implications for better understanding and treating blood cancers. For example, myeloid leukemias, striking mostly older people, affect myeloid blood cells such as granulocytes and monocytes. Camargo thinks these leukemias may originate from blood stem cells, and that leukemias in children, which are mostly lymphoid leukemias, may originate from eMPPs.

We are following up to try to understand the consequences of mutations that lead to leukemia by looking at their effects in both blood stem cells and eMPPs in mice, he says. We want to see if the leukemias that arise from these different cells of origin are different lymphoid-like or myeloid-like.

Finally, the recognition that there are two types of mother cells in the blood could revolutionize bone marrow transplant.

When we tried to do bone marrow transplants in mice, we found that the eMPPs didnt engraft well; they only lasted a few weeks, says Camargo. If we could add a few genes to get eMPPs to engraft long term, they could potentially be a better source for a bone marrow transplant. They are more common in younger marrow donors than blood stem cells, and they are primed to produce lymphoid cells, which could lead to better reconstitution of the immune system and fewer infection complications after the graft.

Reference: Lifelong multilineage contribution by embryonic-born blood progenitors by Sachin H. Patel, Constantina Christodoulou, Caleb Weinreb, Qi Yu, Edroaldo Lummertz da Rocha, Brian J. Pepe-Mooney, Sarah Bowling, Li Li, Fernando G. Osorio, George Q. Daley and Fernando D. Camargo, 15 June 2022, Nature.DOI: 10.1038/s41586-022-04804-z

Sachin H. Patel, MD, PhD, of the Stem Cell Program (now at University of California San Francisco) and Constantina Christodoulou, PhD (now at Bristol Myers Squibb) were co-first authors on the paper. The study was funded by the National Institutes of Health (HL128850-01A1, P01HL13147), the Evans MDS Foundation, the Alex Lemonade Foundation, the Leukemia and Lymphoma Society, and the Howard Hughes Medical Institute. The authors declare no competing interests.

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The Origins of Our Blood May Not Be What We Thought - SciTechDaily

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Srinagar, June 29: In a recent case, doctors at HCMCT Manipal Hospitals, Dwarka successfully treated a 9-year-old patient from Iraq who was suffering from a rare disease called Diamond Blackfan anemia presenting as aplastic anaemia.

She presented with low hemoglobin, low platelets, and low TLC. The team led by Dr. Divya Bansal successfully performed a bone marrow transplant where the donor was the patients 3-year-old sister.

Diamond-Blackfan anemia (DBA) is a rare blood disorder that occurs when the bone marrow fails to make red blood cells, which are essential for carrying oxygen from the lungs to all the other parts of the body. In this case, the patient had a extremely rare presentation of Diamond Blackfan anemia, where her bone marrow was suppressed and she had low hemoglobin, platelets, and TLC.

This was a challenging case as she was platelet transfusion refractory; no matter how many platelets she was given, her platelet count did not rise, and she was bleeding profusely from the nose and mouth, which was life threatening. Transplant in this condition was particularly challenging, as conditioning therapy, which is given before donor stem cell infusion, further depletes the platelets.

Speaking about this case, Dr. Divya Bansal, Consultant of Clinical Hematology and Bone Marrow Transplant, HCMCT Manipal Hospital, Dwarka said, "This was a different case, the little girl was brought to us with a history of weakness and bleeding from the nose and mouth. We evaluated her further and found that she had congenital bone marrow failure syndrome, diamond blackfan anemia. There was a high PNH clone (paroxysmal nocturnal hemoglobinuria), which is another uncommon condition in the general population and even more so in children. She had a congenital cause as well as an acquired cause for aplastic anemia. Luckily, one of her sisters, who was just 3 years old, turned out to be a 100% HLA match for a bone marrow transplant. However, the difference between donor weight and recipient weight was very wide. The recipient was around 40 kg, and the donor was around 12 kg. Generally, a 10% weight difference is accepted. The protocol is that when you have a major weight difference, then the stem cell collection is done in two settings. But due to the time factor, we had to do it in one sitting only."

The patient contracted a dreadful infection at an early stage of the transplant. However, with the assistance of experienced experts and cutting-edge technology at Manipal Hospitals, the patient was successfully treated, and she was engrafted on day 14 of the transplant, and the chimerism was performed on the 30th day. She is now 100 percent donor chimerism, which means that all the cells in her body are from the donor. This was a success story for us because it was a rare disease with exceedingly rare complications and presentation but was done successfully.

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9-year-old Iraqi girl diagnosed with rare blood disorder successfully treated at HCMCT Manipal Hospitals - Rising Kashmir

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An estimated 1,240,000 blood cancer cases emerge annually worldwide, accounting for approximately 6 per cent of all the cancer cases. Meanwhile 720,000 people die of blood cancer every year, accounting for 7 per cent of the cancer deaths.

These statistics were shared by Dr Munira Borhany, haematologist and associate professor at the National Institute of Blood Diseases & Bone Marrow Transplant (NIBD) at a public awareness seminar held recently in collaboration with the Neurospinal & Cancer Care Postgraduate Institute.

The event was titled Rising Burden of Blood Cancers in Pakistan.

"Cancers of blood, bone marrow and lymphatic system are collectively referred to as blood cancers ranging from slow-growing to very aggressive. When the body's red blood cells, white blood cells or platelet production is unusual or abnormal, blood cancer develops. It normally begins in the bone marrow, which is responsible for the production of blood. The normal functioning, growth and development of blood cells that fight infection and make healthy blood cells are disrupted by this type of cancer. There are 137 types of blood cancers and related disorders, she explained, adding that blood cancer was among the most common form of cancers to affect children and adolescents.

The haematologist said that the symptoms of blood cancer could be quite variable depending upon its type. The common symptoms included unexplained fatigue, fever, weakness, and tiredness which could be fast develop in conditions such as acute leukaemia. There may be bleeding manifestations, bone pains, occurrence of swellings in the entire body, loss of appetite, weight loss and abdominal pain, she added.

She said that in general, the symptoms could be quite non-specific such as flu-like symptoms to more dramatic ones such as bleeding manifestations and severe infection. Highlighting the efficacy of bone marrow transplant (BMT) for such patients, she said the BMT was a highly effective therapy and often the only hope for a cure or a longer life for patients with blood cancers.

Dr Munira explained BMT was a procedure to replace disordered bone marrow with healthy bone marrow stem cells. Transplant physicians use this procedure to eliminate cancer or defective stem cells and restore a patient's blood and immune systems.

She added that not all patients with blood cancer required BMT. The need for a bone marrow transplant is evaluated case-wise based on the individual patientss underlying diagnosis, treatment response and disease genetic profile. She informed the event that patients' response to treatment in cases of acute leukemia had improved, due to the cutting-edge genetic profiling technologies combined with innovative medication.

Highlighting the benefits of BMT, Dr Munira said the procedure had two major advantages over other forms of transplants firstly, the donors did not lose any vital part of their body for life and secondly, the recipients had to take the immunosuppressive drug only for nine months.

The bone marrow transplant unit at the NIBD has successfully performed 750 BMT, including 690 allogeneic and 60 autologous blood stem cell transplants with the success rate of more than 80 per cent despite the pressure placed on the healthcare system due to Covid-19 pandemic as well as national economic crisis and escalation of the dollar value against the rupee, she said.

The expert said a bone marrow transplant surgery cost more than Rs4 million in Pakistan but the entire procedure was performed at the NIBD free of charge. She requested the industrial sector, philanthropists and NGOs to support the NIBD for this noble cause.

Blood cancer treatment success rates are improving drastically, and patients are living longer than ever before. There are now various effective and targeted therapeutic agents that have been effective such as chemotherapy, radiotherapy, targeted therapy, bone marrow transplantation and immunotherapy in beating cancer. There is a better chance of a complete cure with early diagnosis, she maintained.

Earlier, NIBD Chief Executive Officer Usama Sultan Shamsi told the seminar that there was a need for increasing awareness among the public as well as medical fraternity to help realise that blood cancer and related disorders were just another forms of disease with a potential for high cure rates provided that they were investigated properly and specific treatment instituted.

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Success rate of blood cancer treatment drastically improving, seminar told - The News International

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First prospective controlled trial in the world on treating chronic back pain with stem cells shows 70% of participants helped by the treatment

Dr. Sairam Atluri has successfully treated more than 400 patients at his StemCures clinic in Cincinnati over the past five years

Proper use of bone marrow mesenchymal stem cells, or BM-MSCs, for chronic pain treatment follows FDA protocols

CINCINNATI, June 15, 2022 /PRNewswire/ --Local Cincinnati pain physician Dr. Sairam Atluri led the first prospective controlled clinical trial on using bone marrow mesenchymal stem cells (BM-MSCs) for chronic pain. 70% of study participants gained significant pain relief and improved physical and mental function. The first of its kind in the world, the study was completed last month in Ohio.

"Evaluation of the Effectiveness of Autologous Bone Marrow Mesenchymal Stem Cells in the Treatment of Chronic Low Back Pain Due to Severe Lumbar Spinal Degeneration: A 12-Month, Open-Label, Prospective Controlled Trial"was published in the official publication of the American Society of Interventional Pain Physicians, Pain Physician Journal. It is the only scientifically accepted controlled study in the world. 15 other physicians participated in the study.

"When I saw the results my patients were getting at my StemCures health facility, I and my colleagues decided the only way to get physicians to accept this treatment as a mainstream therapeutic for chronic pain was to get a study published in a respected journal," said Dr. Atluri. "About 90 percent of physicians have little to no knowledge of this treatment. They, and their patients, need to know."

40 patients were in the BM-MSC treatment group for the study, and 40 were in a control group, receiving traditional pain modalities such as injections, physical therapy, nerve ablations, and pain medications. The research group then followed their progress for one year:

Almost 70% of those receiving BM-MSCs had significant pain relief and improved physical and mental function. All had cut down or eliminated their pain medication.

Only 8% in the controlled group (not receiving BM-MSCs) had any improved functioning.

Story continues

BM-MSC treatment is a constructive pain therapeutic, as the patient's own cells, that are proven to be safe and effective, are extracted and then injected back into the area that needs repair and healing. The painless procedure takes about 90 minutes and is typically performed just one time for each area affected by chronic pain.

According to Dr. Atluri, it's important the public knows what BM-MSCs are, and what they aren't.

Mesenchymal stem cells are designed to repair and heal. They are present in every tissue, ready to spring into action if you cut your finger, or suffer an acute muscle injury.

BM-MSC treatment, done properly, follows allowed FDA protocols.

BM-MSCs are not embryonic or fetal stem cells. There are almost no cell therapies currently performed with these cell types.

These are not amniotic stem cells. This is important because there are many "pseudo clinics" advertising stem cell procedures that use "off-the-shelf" amniotic stem cells. Most are not performed by qualified physicians, are violating FDA protocols, and are a waste of money. They may also adversely affect your health.

BM-MSCs are not hematopoietic stem cells derived from blood platelets for treatments such as leukemia.

Dr. Atluri, who has successfully treated over 400 patients over the last five years at his clinic, also pointed out that by making the treatment more accessible to chronic pain sufferers, more patients can wean themselves off prescription painkillers. The consequences of that could significantly impact this country's opioid addiction problem.

"These results of this treatment are astonishing and now, irrefutable," said Dr. Atluri. "I travel around the world educating and teaching other physicians about BM-MSCs and now I can do it with scientific proof in hand. Every physician treating chronic pain patients should be identifying their BM-MSC candidates, which are those who suffer from arthritis or joint degeneration for more than six months and don't have contraindications such as cancer.

"It's changing people's lives and in many cases, giving them a future to look forward to for the first time in years."

For more information about the study and bone marrow mesenchymal stem cells treatment, contact Dr. Atluri at hisStemCures clinic at 513-624-7525. The clinic address is 7655 Five Mile Rd., Ste. 117, Cincinnati.

Cision

View original content:https://www.prnewswire.com/news-releases/cincinnati-pain-management-physician-leads-first-successful-stem-cell-controlled-trial-with-70-of-participants-seeing-positive-results-301568002.html

SOURCE Dr. Sairam Atluri

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Cincinnati Pain Management Physician Leads First Successful Stem Cell Controlled Trial with 70% of Participants Seeing Positive Results - Yahoo...

Bone Marrow Stem Cells Comments Off on Cincinnati Pain Management Physician Leads First Successful Stem Cell Controlled Trial with 70% of Participants Seeing Positive Results – Yahoo… | June 20th, 2022

Symptoms of the disease are usually visible at the age of 5 months and change over time. Some of the common symptoms include pain, anaemia, frequent infections, swelling of hands and feet and vision problem

Sickle-shaped cells and normal blood cells in human blood. Image courtesy: Wikimedia Commons/Dr Graham Beards

World Sickle Cell Day is marked every year on 19 June with an aim to raise awareness about sickle cell disease. Sickle Cell Disease is a group of disorders that impact haemoglobin, the molecule in red blood cells which deliver oxygen to cells throughout the body.

Individuals who live with this disease have haemoglobin S, an atypical haemoglobin molecule which distorts red blood cells into a sickle or a crescent shape. The disease is usually transmitted from parents to children.

What are the symptoms?

Symptoms of the disease are usually visible at the age of 5 months and change over time. Some of the common symptoms include pain, anaemia, frequent infections, swelling of hands and feet and vision problem.

What are the different types of Sickle Cell Disease?

If one of the parents has a problem gene, then the child will not have symptoms but will possess sickle cell trait.

What is the treatment?

The disease can be detected in an infant during the screening process of a newborn. In case, there is a family history of the Sickle Cell disease, it can even be diagnosed at the time of pregnancy.

The only way to cure it is either stem cell or a bone marrow transplant. The symptoms can also be dealt with the use of antibiotics, periodic blood transfusion, pain killers, and vaccinations.

Read all the Latest News, Trending News,Cricket News, Bollywood News,India News and Entertainment News here. Follow us on Facebook, Twitter and Instagram.

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World Sickle Cell Day 2022: Know all about symptoms and treatment of the disease - Firstpost

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-- First Site Will Enroll First Patient in the Clinical Study--

MELVILLE, NY., June 13, 2022 (GLOBE NEWSWIRE) -- BioRestorative Therapies, Inc. (the Company or BioRestorative) (NASDAQ: BRTX), a clinical stage company focused on stem cell-based therapies, today announced site initiation for its Phase 2 clinical trial targeting chronic lumbar disc disease (cLDD). The Denver Spine and Pain Institute is the first clinical site to be initiated. Additional selected sites are expected to be initiated in 2022.

BioRestoratives Phase 2 trial is a double-blind controlled, randomized study to evaluate the safety and preliminary efficacy of a single dose intradiscal injection of the Companys autologous investigational stem cell-based therapeutic, BRTX-100. A total of up to 99 eligible patients will be randomized at up to 15 centers in the United States to receive either the investigational drug (BRTX-100) or control in a 2:1 fashion.

Currently there are no approved, cell-based therapies for cLDD. While there is encouraging data that suggests that patients with cLDD could benefit from autologous stem cell transplants, the low oxygen micro-environment of the disc makes cell-based therapies challenging. BRTX-100 is manufactured under low oxygen conditions and engineered to survive this environment, said Scott Bainbridge, M.D., Principal Investigator for the BRTX-100 trial at The Denver Spine and Pain Institute. Positive proof-of-concept data in this trial could be disruptive and support the potential applicability of BRTX-100 to other spine and musculoskeletal disorders where low oxygen micro-environments are found.

We are pleased to initiate the first of several sites across the United States that will be enrolling for the trial, said Lance Alstodt, Chief Executive Officer of BioRestorative Therapies. Our sites have been carefully reviewed and selected and have clinical expertise in treating patients who could potentially benefit from BRTX-100. We look forward to working with the principal investigators and their clinical trial teams.

About BioRestorative Therapies, Inc.

BioRestorative Therapies, Inc. (www.biorestorative.com) develops therapeutic products using cell and tissue protocols, primarily involving adult stem cells. Our two core programs, as described below, relate to the treatment of disc/spine disease and metabolic disorders:

Forward-Looking Statements

This press release contains "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, and such forward-looking statements are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. You are cautioned that such statements are subject to a multitude of risks and uncertainties that could cause future circumstances, events or results to differ materially from those projected in the forward-looking statements as a result of various factors and other risks, including, without limitation, those set forth in the Company's latest Form 10-K filed with the Securities and Exchange Commission and other public filings. You should consider these factors in evaluating the forward-looking statements included herein, and not place undue reliance on such statements. The forward-looking statements in this release are made as of the date hereof and the Company undertakes no obligation to update such statements.

CONTACT:Email: ir@biorestorative.com

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BioRestorative Therapies Announces Clinical Site Initiation for the Company's Phase 2 Clinical Trial to Treat Chronic Lumbar Disc Disease (cLDD) -...

Bone Marrow Stem Cells Comments Off on BioRestorative Therapies Announces Clinical Site Initiation for the Company’s Phase 2 Clinical Trial to Treat Chronic Lumbar Disc Disease (cLDD) -… | June 20th, 2022

MarketQuest.biz has announced the addition of new research titled Global Rheumatoid Arthritis Stem Cell Therapy Market from 2022 to 2028, which encompasses regional and global market data and is predicted to generate attractive valuation.The Rheumatoid Arthritis Stem Cell Therapy research covers market drivers, opportunities, limiting factors, and barriers. It provides a quantitative market study based on annual reports, product literature, industry announcements, and other sources.

The report explains the market definition, classifications, applications, engagements, and global Rheumatoid Arthritis Stem Cell Therapy industry trends are.It gives a realistic picture of the current market position incorporating original and predicted market estimates.The report gives a thorough analysis of their product portfolios to investigate the products and applications they focus on while working in the worldwide Rheumatoid Arthritis Stem Cell Therapy market. The report offers valuable suggestions to new just as set up players of the market.

DOWNLOAD FREE SAMPLE REPORT: https://www.marketquest.biz/sample-request/121261

In order to improve industrial planning, data points such as flow patterns, openings, drivers, limits, and statistics are acquired from trusted sources. The data and numbers in the research report have been provided comprehensively, using graphical and pictorial representations to understand the market better.Further when datais synthesised, statistical analysis takes place. Several processes, including screening, integration, and data extrapolation, must be performed prior to data validation.

The product types covered in the report include:

The application types covered in the report include:

The countries covered in the market report are:

The key and emerging market players in the global market include:

ACCESS FULL REPORT: https://www.marketquest.biz/report/121261/global-rheumatoid-arthritis-stem-cell-therapy-market-2022-by-company-regions-type-and-application-forecast-to-2028

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This report can be customized to meet the clients requirements. Please connect with our sales team (sales@marketquest.biz), who will ensure that you get a report that suits your needs. You can also get in touch with our executives on 1-201-465-4211 to share your research requirements.

Contact UsMark StoneHead of Business DevelopmentPhone: 1-201-465-4211Email: sales@marketquest.biz

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Global Rheumatoid Arthritis Stem Cell Therapy Market 2022 Swot Analysis by Top Key Vendors, Demand And Forecast Research to 2028 Designer Women -...

Bone Marrow Stem Cells Comments Off on Global Rheumatoid Arthritis Stem Cell Therapy Market 2022 Swot Analysis by Top Key Vendors, Demand And Forecast Research to 2028 Designer Women -… | June 20th, 2022

Abstract: Background Avascular necrosis of the femoral head (ANFH) is a common orthopaedic disease due to bone defects. However, few clear methods to treat ANFH in clinical practice are known. Many findings suggest that promoting the osteogenic differentiation and directional migration of stem cells may be a key method for bone regeneration. Over time, an increasing number of researchers have begun to focus on Chinese medicine and Chinese medicinal extracts; Epimedium is the Chinese herbal medicine studied in the most detail in the field of bone regeneration, and Icariin (ICA) is one of the main active ingredients in Epimedium. Objective This study aimed to explore the effects of ICA on the osteogenic differentiation and migration of bone marrow mesenchymal stem cells (BMSCs) and reveal its mechanism to provide a theoretical basis for the treatment of ANFH. Methods After primary BMSCs were freshly isolated from a normal rabbit and treated with various concentrations of ICA, the activity and proliferation of BMSCs were detected by CCK-8 assay, and the mineralized nodules was detected by Alizarin Red staining, to determine the optimal concentration of ICA. qPCR and western blot were used to demostrate the effects of ICA on the osteogenic differentiation and migration of BMSCs. Osteoblasts-derived exosomes (OB-exos) were extracted and analysed by high-throughput sequencing. Effect of ICA combined with OB-exos were analysed. And miRNA mimic and an miRNA inhibitor were synthetised to verify the osteogenic differentiation and migration of BMSCs alone or co-cultured with ICA. Results The CCK-8 assay and Alizarin Red staining showed that the optimal concentration of ICA is 1107 M. ICA could effectively promote the osteogenic differentiation and migration of BMSCs, and this could be enhanced after co-culturing with OB-exos. The four miRNAs with the greatest concentrations in the OB-exos were let-7a-5p, miR-100-5p, miR-21-5p and miR-122-5p. qPCR and western blot showed that miR-122-5p mimic has positive effects on the osteogensis and migration, and its inhitiotr has negative effects. Simliarly, they could enhance or inhitor the effects of ICA, which means miR-122-5p may be the target of ICA. Conclusion Like the OB-exos, ICA could obviously promote the osteogenic differentiation and migration of BMSCs. The combination of ICA and OB-exos enhanced these effects, in which miR-122-5p plays a pivotal role.

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Mechanism of Icariin regulation of the effect of miR-122-5p in osteoblast-derived exosomes on osteogenesis and migration of bone marrow mesenchymal...

Bone Marrow Stem Cells Comments Off on Mechanism of Icariin regulation of the effect of miR-122-5p in osteoblast-derived exosomes on osteogenesis and migration of bone marrow mesenchymal… | June 11th, 2022

A new study has identified a possible target for treating juvenile myelomonocytic leukemia, a highly aggressive blood cancer.

Research into a type of blood cancer called juvenile myelomonocytic leukemia suggests anti-inflammatory treatment as a possible new therapy for the disease

Juvenile myelomonocytic leukemia (JMML) is most common in children under the age of four. 10% of all cases occur in newborns under the age of three months. Every year, one to two children out of a million are diagnosed with JMML. The disease accounts for approximately 1.6 percent of all blood-related cancers. It is more common in males, with boys being nearly twice as likely as girls to develop JMML.

The exact underlying causes of JMML are unclear, however, virtually all patients will have a mutation in a RAS gene or a gene that affects the activation levels of Ras proteins that modifies the DNA within their blood cells. Currently, allogeneic hematopoietic stem cell transplantation is the only successful treatment for the majority of patients, although recent advancements show promise.

According to a report published on May 10th, 2022, in the journal eLife, scientists have identified a potential new target for treating patients with the blood cancer juvenile myelomonocytic leukemia (JMML).

Their findings in zebrafish and JMML patients suggest that anti-inflammatories may be a new approach to fighting the disease.

JMML is a highly aggressive blood cancer with poor patient outcomes. Children with Noonan Disease (NS), a relatively common developmental syndrome, are at a high risk of having a disorder similar to JMML called myeloproliferative neoplasm, which may later progress to JMML. A mutation in the PTPN11 gene, which encodes the protein-tyrosine phosphatase SHP2, is the most common genetic cause of JMML and NS.

Hematopoietic stem and progenitor cells are considered to be the cells of origin for JMML, says first author Maja Solman, Postdoctoral Fellow at the Hubrecht Institute, Utrecht, Netherlands. Currently, hematopoietic stem cell transplantation is the only treatment for the disease, but it has a relapse rate of 50%. With such limited treatment options for JMML, we wanted to gain a better understanding of how the disease develops to identify other possible ways of targeting it.

This image shows the macrophages (red) and neutrophils (green) in a zebrafish embryo with a mutation in SHP2. The head of the embryo is on the left, the tail on the right. Similar to the situation in JMML patients, this fish has more macrophages and neutrophils compared to fish without a mutation in SHP2. Credit: Maja Solman

To do this, Solman and the team used a novel zebrafish model with a mutation in SHP2 equivalent to the most common mutation in NS patients which can cause JMML. They used a technique called single-cell transcriptomics to examine the level of gene expression in the animals hematopoietic stem and progenitor cells. The analysis showed an increase in the number of monocyte and macrophage progenitor cells in the fish embryos, and that these cells expressed genes associated with the immune response.

The team next compared these results with their analysis of hematopoietic stem and progenitor cells, which contained SHP2 mutations, from the bone marrow of JMML patients. They found a similar pattern of proinflammatory gene expression in these cells to the one they identified in the zebrafish.

Finally, they treated the zebrafish embryos with an anti-inflammatory drug called dexamethasone. They found that the drug helped rescue JMML-like blood defects in the fish, suggesting that anti-inflammatories could one day be an important treatment strategy for JMML.

Our work reveals striking similarities in the proinflammatory response of human and zebrafish cells containing SHP2 mutations, and shows that inhibiting this response can improve JMML-like symptoms in a zebrafish model, concludes senior author Jeroen den Hertog, Group Leader and Managing Director at the Hubrecht Institute, and Professor of Molecular Developmental Zoology at Leiden University, Netherlands. Together, these findings lay the groundwork for future studies to verify the effectiveness of anti-inflammatories as a potential new treatment approach for JMML patients.

Reference: Inflammatory response in hematopoietic stem and progenitor cells triggered by activating SHP2 mutations evokes blood defects by Maja Solman, Sasja Blokzijl-Franke, Florian Piques, Chuan Yan, Qiqi Yang, Marion Strullu, Sarah M Kamel, Pakize Ak, Jeroen Bakkers, David M Langenau, Hlne Cav and Jeroen den Hertog, 10 May 2022, eLife.DOI: 10.7554/eLife.73040

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New Treatment for Highly Aggressive Blood Cancer - SciTechDaily

Bone Marrow Stem Cells Comments Off on New Treatment for Highly Aggressive Blood Cancer – SciTechDaily | June 11th, 2022

Myeloproliferative neoplasms (MPNs) are a diverse group of chronic hematological diseases caused by the clonal expansion of abnormal hematopoietic stem cells, of which polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) have been extensively studied in terms of clonal expansion, fibrosis, and other phenotypes. For a study, researchers sought to evaluate current research on the impact of different types of MPN on bone health.

Human data were used in research to show that different types of MPN influence bone density, osteoblast proliferation, and differentiation. The majority of data revealed that bone volume is frequently raised in patients with PMF. In contrast, it was slightly decreased or not affected in patients with ET or PV; however, probable distinctions between male and female phenotypes in most MPN subtypes have not been thoroughly examined.

Osteosclerosis in PMF patients was a significant consequence that could result in bone marrow failure, and bone loss seen in some ET or PV patients can result in osteoporotic fractures. Some MPN types were associated with an increase in the number of megakaryocytes (MKs), and various MK-related MPN variables are known to impact bone formation.Investigators discussed known mechanisms involved in the processes, emphasizing the function of MKs and secreted factors. Understanding MPN-related alterations in bone health should lead to better early intervention and treatment of this pathologys adverse effects.

Reference:ashpublications.org/blood/article-abstract/139/21/3127/476662/Myeloproliferative-disorders-and-their-effects-on?redirectedFrom=fulltext

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Myeloproliferative Disorders & Bone Homeostasis: The Role of Megakaryocytes - Physician's Weekly

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The new report by Expert Market Research titled, Global Live Cell Imaging Market Report and Forecast 2022-2027, gives an in-depth analysis of the global live cell imaging market, assessing the market based on its segments like product type, application, technology, and major regions. The report tracks the latest trends in the industry and studies their impact on the overall market. It also assesses the market dynamics, covering the key demand and price indicators, along with analysing the market based on the SWOT and Porters Five Forces models.

Request a free sample copy in PDF or view the report [emailprotected] https://bit.ly/3mtMGEU

The key highlights of the report include:

Market Overview (2017-2027)

As the number of stem cell research projects grows, so does the use of live cell imaging tools to analyse the location, purity, and amount of cells and their components, boosting market growth. The use of live cell imaging tools to precisely detect protein levels for optimal medication therapy is rising, as it is critical to determine the interaction between stem cells and tissues during stem cell research. The introduction of numerous government initiatives to support research and development (R&D) activities is fueling the live cell imaging industrys expansion. For example, in March 2020, the Canadian government announced a $6.9 million investment to promote stem cell research efforts in the country through the Stem Cell Networks research financing programme.

Furthermore, the increasing use of live cell imaging in the discovery of new medications is propelling the market forward. The development of new technologies that allow for the precise analysis of RNA, nucleic acid, proteins, and DNA, among other things, is driving demand for many diagnostic methods, moving the market forward. Furthermore, the rise in the prevalence of chronic diseases like cancer is driving up demand for live cell imaging in both diagnosis and treatment. The expanding research and development (R&D) activities to detect cancer cells in bone marrow while also allowing for the identification of specific cancer cells are likely to boost market growth.

Industry Definition and Major Segments

The study of living cells using microscope technology to obtain images of live cells and tissues is known as live cell imaging. It is essential in a variety of laboratory operations in biological and biomedical research because it gives real-time and reliable information on cells and tissues, making it suitable for stem cell research and regenerative medicine development.

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By technology, the market can be divided into:

The market can be categorised based on its applications into:

The major product types of live cell imaging are:

The regional markets include:

Market Trends

Artificial intelligence (AI), deep learning, and 3D printing are progressively being integrated into live cell imaging techniques, as technology improvements are a key antecedent of scientific research and development efforts. The expanding use of artificial intelligence (AI) allows for more precise, simpler, and time-efficient cell imaging. Furthermore, AI-based microscopy can recognise and analyse minor cell components like nuclei, allowing researchers to analyse data more quickly and effectively. AI-based microscopes also automate and optimise many functions for quantifying live cells, resulting in increased cell viability and faster image capture. This is fueling the expansion of the live cell imaging sector by increasing demand for such microscopes in research centres.

Furthermore, the increasing use of 3D printing in a variety of medical and biological applications is fueling market expansion. Because air bubbles are a common problem in perfusion chambers used in live cell imaging, the demand for fluidic devices made with 3D printing technology is increasing dramatically. Furthermore, the cost-effectiveness of 3D printing is increasing the affordability of live cell imaging research operations, which is propelling the market forward. In the forecast future, the development of portable and low-profile devices that can be directly installed on optical microscopes to improve cell imaging precision is expected to drive market expansion for live cell imaging.

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Key Market Players

The major players in the market are Carl Zeiss AG, Leica Microsystems GmbH, Nikon Instruments Inc., Becton, Dickinson and Company, GE Healthcare and Others.

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Global Live Cell Imaging Market to be Driven by Growing Stem Cell Research Market in the Forecast Period of 2022-2027 mbu timeline - mbu timeline

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Pervez Musharraf served as Pakistan's president from 2001 to 2008.

The family of former Pakistan President Pervez Musharraf (retired) has said that he has been hospitalised for the last three weeks after his condition worsened. In a statement posted on Twitter on Mr Musharraf's official Twitter account, his family said that he is dealing with Amyloidosis and prayed for ease in his daily living.

"He is not on the ventilator. Has been hospitalized for the last 3 weeks due to a complication of his ailment (Amyloidosis). Going through a difficult stage where recovery is not possible and organs are malfunctioning. Pray for ease in his daily living," the tweet said.

According to National Health Service (NHS) of the UK, Amyloidosis is the name for a group of rare, serious conditions caused by a build-up of an abnormal protein called amyloid in organs and tissues throughout the body.

Amyloid deposits can build up in the heart, brain, kidneys, spleen and other parts of the body.

The build-up of these protein deposits can make it difficult for the organs and tissues to work properly. Without treatment, this can lead to organ failure, the NHS further said.

Mr Musharraf was diagnosed with the life-threatening health condition in 2018 in the UAE.

Amyloidosis may be secondary to a different health condition or can develop as a primary condition, according to Johns Hopkins Medicine. Sometimes it is due to a mutation in a gene, but other times the cause of amyloidosis remains unknown, it added.

There are different types of the Amyloidosis, which are prevalent:

Light-chain (AL) Amyloidosis: It can affect the kidneys, spleen, heart, and other organs. People with conditions such as multiple myeloma or a bone marrow illness called Wadenstrom's macroglobulinemia are more likely to have AL amyloidosis.

AA Amyloidosis: It is caused by fragments of amyloid A protein, and affects the kidneys in about 80 per cent of cases. It can complicate chronic diseases characterized by inflammation, such as rheumatoid arthritis (RA) or inflammatory bowel disease (IBS).

Transthyretin Amyloidosis (ATTR): It can be inherited from a family member. Transthyretin is a protein that is also known as prealbumin. It is made in the liver. Excessive normal (wild-type ATTR) or mutant transthyretin can cause amyloid deposits.

Though there are some common symptoms of the disease, they vary greatly depending on where the amyloid protein is collecting in the body.

The general symptoms include (listed by Johns Hopkins on its website):

As Amyloidosis progresses, the deposits of amyloid can harm the heart, liver, spleen, kidneys, digestive tract, brain or nerves.

The diagnosis of Amyloidosis is hard, as the symptoms are generic. The doctors take a small sample of the tissue (biopsy) from the affected part to understand what kind of Amyloidosis is present. Depending on that, the treatment is done.

There is not currently a cure for amyloidosis. The amyloid deposits cannot be directly removed. So the doctors may discuss:

Chemotherapy, which is used to kill cancer cells or stop them from growing and similar method can be adopted to stop the growth of cells that are making abnormal protein.

Bone marrow transplant: In this procedure, healthy stem cells are taken from a patient's body. They are then infused back into their body to replace the unhealthy ones destroyed in chemotherapy.

There are some medicines too, which are used to treat Amyloidosis. These medicines are approved by the Food and Drug Administration (FDA) in the United States.

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The BioIntelliSense BioSticker. Photo courtesy of BioIntelliSense.

James Byrne hadnt been out of the hospital for long when a call came in after midnight. He answered to the voice of a triage nurse asking him how he was feeling. He was pretty tired, actually, having been through radiation treatment and chemotherapy designed to eradicate his acute myeloid leukemia and then an allogeneic bone marrow transplant (his son Logan had been the key donor; his cells were augmented with donated umbilical-cord stem cells). That and having been asleep until his cell phone rang. But otherwise, just fine, he said.

Good to hear, the nurse said because Byrnes body temperature had just jumped to 98.9 degrees. While thats just a shade higher than the standard 98.6 degrees, his temperature had been hanging around 97 degrees, so what would otherwise seem normal might instead have been an indication of a brewing infection. Given that his immune system had been wiped out and was just starting to rebuild itself, an infection would pose a serious risk to the 45-year-old resident of Albuquerque, N.M. This was, fortunately, a red flag that could be safely lowered again.

Byrne would have had a hard time taking his own temperature while sound asleep. A three-inch by one-inch, U.S. Food and Drug Administration-approved medical device called a BioSticker had done that and much more.

Before Byrne left UCHealth University of Colorado Hospital on the Anschutz Medical Campus, the UCHealth and University of Colorado School of Medicine advanced practice practitioner leading the study, Glen Peterson, had asked him if he might be interested in joining one of two cancer-related clinical trials using the remote-monitoring gadget developed by Golden-based BioIntelliSense. This one would involve sticking the BioSticker to his upper chest and largely forgetting about it for 30 days. The BioSticker would collect a steady stream of his vital signs body temperature, respiratory rate, resting heart rate, skin temperature, gait, body position and more and transmit it to UCHealth providers via a wireless hub and Reimagine Care, a startup focused on home cancer care. The goal would be to spot emerging health problems before Byrne himself did.

Its not the first work UCHealth has done with BioIntelliSense. Their collaborations through the UCHealth CARE Innovation Center have most notably involved remote monitoring of high-risk COVID-19 patients. But Dr. Richard Zane, UCHealths chief innovation officer and chair of the CU School of Medicines Department of Emergency Medicine, says the technology could apply to a wide range of health conditions.

Its about bringing remote patient monitoring to wherever the patient is, understanding how to ingest key vital signs, and building predictive and prescriptive algorithms on top of those data so that we can intervene before we otherwise would have, Zane said.

Technologies such as BioIntelliSenses BioSticker and the recently announced BioButton an even-smaller stick-on medical device that captures much of the same data as its predecessor have the potential to supplant an outdated system of discharged patients self-reporting their own health status, as Dr. Clay Smith, director of the UCHealth Blood Disorders and Cell Therapies Center and associate chief of the CU School of medicines Division of Hematology, put it.

Byrnes example of having a lower-than-usual body temperature is a case in point. The typical approach of having people take their temperature a couple of times a day and report fevers to caregivers assumes 98.6 as the normal temperature. But it can vary from person to person, as it did with Byrne; it can be lowered by medications; it can go up on a hot day or even when wearing a hat. A long-term monitoring device such as the BioSticker, which captures and transmits 1,440 measurements every 24 hours, day and night, can establish baselines from which to judge abnormalities.

We see people who are quite ill who have a normal temperature and those with a higher temperature who are fine, Smith said.

The second UCHealth-BioIntelliSense study also relates to body temperature. That study, which Peterson also leads, involves cancer patients whose chemotherapy has left them with low numbers of white blood cells called neutrophils that help fight infections. These patients are susceptible to febrile neutropenia a fever caused by an infection that exploits the weakened immune system. Febrile neutropenia cases account for about 5% of all adult cancer-related hospitalizations in the United States, with an average stay of more than eight days.

The sooner one can spot a fever or other signs of nascent illness, the faster the patient can get treatment.

We know that, the longer you wait from the time infection starts, the worse the outcomes, Smith said. Its important to detect it as soon as possible, figure out what type of infection it is, and start antibiotics.

Fevers are only the beginning, Smith says. He sees technologies such as the BioSticker feeding diverse readings into artificial-intelligence-powered systems capable of synthesizing body temperature, heart rate, respiratory rate, movement characteristics, and other factors to detect a whole range of problems and alert health care providers to nip health problems in the bud.

Zane says BioIntelliSenses work with UCHealth is already moving in that direction. Theyve identified patterns in the data that seem to predict fevers while a patients temperature is still normal. Such insight could one day let providers prescribe antibiotic pills for patients at home to beat back infections before theyre serious, thereby avoiding hospitalization for intravenous antibiotics.

James Byrnes BioSticker has triggered a few calls over the month he has worn it, he says. One involved a 3:30 a.m. call from a nurse practitioner triggered by a change in his breathing patterns and indeed, he had been coughing for much of the night. The nurse had him check his pulse oxygen level; it was normal.

Another had to do with a leap in his heart rate. He happened to have been walking around quite a bit at the time, he says, and he isnt in the best shape of his life for obvious reasons. The triage nurse explained why she was calling and asked, You doing alright?

Im doing just fine, he answered.

But it was nice to get that call.

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TAIPEI--(BUSINESS WIRE)--PharmaEssentia Corporation (TPEx:6446), a global biopharmaceutical innovator based in Taiwan leveraging deep expertise and proven scientific principles to deliver new biologics in hematology and oncology, today announced a series of data presentations will illustrate outcomes with ropeginterferon alfa-2b (marketed as BESREMi) among adults with polycythemia vera (PV) during the European Hematology Associations Hybrid Congress (EHA2022), June 9-17 in Vienna, Austria.

Ongoing evaluations of ropeginterferon alfa-2b expand the depth and duration of data on this innovative therapeutic supporting its ability to control the effects of polycythemia vera (PV), said Albert Qin, MD, PhD, Chief Medical Officer, PharmaEssentia. We believe these important new data offer greater clarity and confidence to physicians that this therapeutic tool represents an approach to effectively and durably treat PV.

Ropeginterferon alfa-2b presentations during EHA2022 will include:

The data presentation regarding the final results of studies leading to marketing authorization of BESREMi in Europe are a result of clinical development work of AOP Health, Vienna. PharmaEssentia has licensed ropeginterferon alfa-2b in Europe to AOP.

About Polycythemia Vera

Polycythemia Vera (PV) is a cancer originating from a disease-initiating stem cell in the bone marrow resulting in a chronic increase of red blood cells, white blood cells, and platelets. PV may result in cardiovascular complications such as thrombosis and embolism, and often transforms to secondary myelofibrosis or leukemia. While the molecular mechanism underlying PV is still subject of intense research, current results point to a set of acquired mutations, the most important being a mutant form of JAK2.1

About BESREMi (ropeginterferon alfa-2b)

BESREMi is an innovative monopegylated, long-acting interferon. With its unique pegylation technology, BESREMi has a long duration of activity in the body and is aimed to be administered once every two weeks (or every four weeks with hematological stability for at least one year), allowing flexible dosing that helps meet the individual needs of patients.

BESREMi has orphan drug designation for treatment of polycythemia vera (PV) in adults in the United States. The product was approved by the European Medicines Agency (EMA) in 2019, in the United States in 2021, and has recently received approval in Taiwan and South Korea. The drug candidate was invented by PharmaEssentia and is manufactured in the companys Taichung plant, which was cGMP certified by TFDA in 2017 and by EMA in January 2018. PharmaEssentia retains full global intellectual property rights for the product in all indications.

BESREMi was approved with a boxed warning for risk of serious disorders including aggravation of neuropsychiatric, autoimmune, ischemic and infectious disorders.

About PharmaEssentia

PharmaEssentia Corporation (TPEx: 6446), based in Taipei, Taiwan, is a rapidly growing biopharmaceutical innovator. Leveraging deep expertise and proven scientific principles, the company aims to deliver effective new biologics for challenging diseases in the areas of hematology and oncology, with one approved product and a diversifying pipeline. Founded in 2003 by a team of Taiwanese-American executives and renowned scientists from U.S. biotechnology and pharmaceutical companies, today the company is expanding its global presence with operations in the U.S., Japan, China, and Korea, along with a world-class biologics production facility in Taichung. For more information, visit our website.

1 Cerquozzi S, Tefferi A. Blast Transformation and Fibrotic Progression in Polycythemia Vera and Essential Thrombocythemia: A Literature Review of Incidence and Risk Factors. Blood Cancer Journal (2015) 5, e366; doi:10.1038/bcj.2015.95.

2022 PharmaEssentia Corporation. All rights reserved.

BESREMi and PharmaEssentia are registered trademarks of PharmaEssentia Corporation, and the PharmaEssentia logo is a trademark of PharmaEssentia Corporation.

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New Data on Ropeginterferon Alfa-2b to Be Featured at EHA2022 - Business Wire

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InThe Moment, a new podcast series from The Athletic,Kelly Cates and Geoff Thomas speak to sportspeople about experiencing and overcoming times of adversity that changed their lives forever.

In this weeks episode, former England footballer Thomas discusses his own recovery from leukaemia and his determination to raise millions of pounds for blood cancer research by completing the route of cyclings arduous Tour de France, just 18 months after undergoing a stem cell transplant.

When Geoff Thomas was told he had three years to live, it seemed like a lifetime.

Just 24 hours earlier, hed believed it was no more than three months.

It was July 2003 and the former Crystal Palace, Wolves and England footballer had been diagnosed with chronic myeloid leukaemia. Id only been retired from football about six to eight months, he says. Id started suffering from fatigue and I was having night sweats and various things but, a typical man, was putting off going to see a doctor.

On the morning of July 4, Thomas finally went to see his doctor. Blood was taken for testing and he was sent home with the message that the results would come back in three weeks time.

About three or four hours later, I got the phone call that changed my life. It was a call that told me I had a form of leukaemia. I was told I could be in the blast phase which, when I stupidly went on the internet, meant it looked like I could only have three months to live.

The following day, Thomas was introduced to bone-marrow specialist Professor Charlie Craddock, who attached him to a machine which helped confirm that, in fact, he had three years to live. The only slim chance of him surviving his leukaemia was to find a stem cell match for a transplant.

Back in 2003, chronic myeloid leukaemia was more or less a death sentence if you couldnt find a match to have a stem cell transplant. And thats only 20 per cent of the population that can do that.

When youre told the brutal honesty about whats ahead of you, you know, the chances of you not surviving is really pretty high. So youre looking for any positives to put you on that positive track.

I read a book about Lance Armstrongs journey the second day I was diagnosed, and I know his name has been tarnished since (Armstrong was stripped of his seven Tour de France and banned from pro cycling for life for doping offences), but his fightback and his desperation to find the best way of surviving his cancer put me on that track. I wanted to turn every stone to give myself the opportunity of surviving this.

Its almost 19 years now since that diagnosis but, mentally and emotionally, Thomas can put himself back on that ward in an instant. I can know exactly what the conversations were and exactly how myself and my wife were handling it: not very good for the first three days, but we had to protect our 10- and seven-year-old little girls, and make sure they were OK.

For the next couple of weeks from being diagnosed, I was looking at what their future looked like without me, to be honest. I was looking to see if they were insured properly, if the house was safe if I disappeared. That was extra comfort, but Ive realised that so many other people dont have that opportunity.

Four days after he was diagnosed, Thomas sister Kay went for blood tests to see if she was a stem cell match. It would take over a month for the results to come back and they were told there was just a one-in-five chance she would be suitable. In the meantime, Thomas and wife Julie made a list of trips they wanted to go on with their two girls. We went off to places like Disneyland Paris and just tried to shield them as much as we could by enjoying ourselves.

Bizarrely, I was in a really good space in my mind because for the first time I realised what was really important in life. And it wasnt the fast cars, it wasnt the bigger house, it wasnt getting a bigger garden. It was just purely your health and your family and being able to be around them.

Thats something I try to keep. When Im starting to have little down days, I try and keep that message within that things could be a hell of a lot worse.

Thomas was fortunate that Kay was a match. Not a very good match, he qualifies. So the doctors had to do some tweaking. But it was good enough for me to go into isolation for five to six weeks and really be beaten up with chemotherapy and radiotherapy. They more or less take everything down to ground level and build you back up again. You purely put your life in the hands of the great guys and nurses at the hospital.

He was put on an intensive course of chemotherapy and radiotherapy to prepare his body for the transplant. At that point, he says your immune system is gone. A simple cold could kill you. Then, all of a sudden, they bring this bag in. Its only about eight inches long, and its just full of a browny, horrible colour.

They hang it up on the little pole and you see it going down the tube and going through your body that was my sisters stem cells. It took a good eight hours to be put in.

The next day, I was really, really poorly. The nurses warned Julie, It doesnt look good. Hes been struggling. And it was probably the lowest point of everything I went through. I didnt think I was going to make it. But Julie just put her arm around me and gave me a hug for about a couple of hours.

After a few days, there were indications that his immune system was starting to work. It was a positive sign. But it would take around six months for Thomas to feel normal again.

It was January 2004 when Thomas had the transplant, and a year later when he received the momentous news that he was in remission, albeit with the knowledge that the treatment hed received could put him at risk of developing different cancers later in life.

The attitude and mentality he developed during a 20-year long football career has played a key role in helping Thomas through the difficult times he suffered. In football, youve got to have good coaches. Youve got to have good trainers to make you the sportsperson you become, he says. But most importantly, you need to have your own determination to make that happen and to be willing to keep learning and keep improving on everything.

Theres so many parallels; the manager turned into the professor. Your team-mates turned into fellow patients. And the nurses were coaches.

And so my mindset was not to try and say, Im going to beat this. I was being honest with everybody. I said, I dont know if Im going to. Like in football, I dont know if were going to win on Saturday, but well try our damnedest to make sure that we do everything to get a good result.

In sport, you find that any negative thought is detrimental to your performance on the Saturday. And I think any negative thought when youre battling an illness is detrimental to your battle as well.

Ive even seen people who have had a positive outcome not able to move away from the illness itself, so they live with that journey theyve been on. And rather than taking it into a positive, theyve kept it like a shroud of darkness around them. Its tough watching these sorts of people.

Thomas still has days when the enormity of what he faced gives him the shivers. It hits me when I see other people going through it, he says. Selfishly, I dont sometimes respond to their story its like it brings my story back. There probably were times where I should have been a lot more open about my feelings but I wasnt. I just buried it.

Ive met a number of footballers who have been touched with blood cancer since. Stiliyan Petrov I met when he was just diagnosed and I just said, Listen, open yourself up to everybody and let your emotions out, because I didnt cry for a while and I felt so much better when I did.

From almost the minute he was diagnosed, Thomas was looking for ways to utilise the profile he had from football to help those who were helping him. On the second day after he met Professor Craddock, he asked him what he could do. I always remember his answer, Thomas says. Let me get you better first, then Ill come back to you. And thats what hes been doing ever since.

A sponsored run or walk is the first port of call for most people who want to find a way to say thank you to the doctors and nurses who have helped them. But as a former professional footballer, Thomas felt he needed to do something more.

Hed already seen former England cricketer Sir Ian Botham walk hundreds of miles to raise funds for leukaemia research and the competitive streak in him told him he needed to surpass that.

A good friend of mine now, Neil Ashton, was following my story he was a reporter back then. He said, Why dont you do the Tour (de France)?. I didnt know what the Tour was, really. I watched it now and then without knowing what was really going on.

Thomas said hed think about it and get back to him. That was February 2005. Id gone into remission in January 2005. And by July, I was doing exactly the same mileage as a professional cyclist just a hell of a lot slower. I found myself doing nearly two and a half thousand miles on a bike and riding some horrendous climbs in the Alps and the Pyrenees.

That was the moment I got my life back. There were stages in there that were so tough that it definitely brought tears to my eyes. But the strength I took on was of the people Id met over the previous two years who hadnt made it; all these stories Ive got deep in the back of my mind.

They always come to the fore when Im going through a little struggle myself, because these people would love to be in my situation when I was going up these climbs. Theyre the people I still call on now and then to keep me going.

Was it medically advisable to put his body through such an intense experience: 21 stages and 2,233 miles? Thomas smiles. Charlie said that in a similar sort of timeline, people normally come and ask him, Is it OK to start swimming?.

He raised over 150,000 that year from cycling the Tour route, and two years later set up the Geoff Thomas Foundation to fund clinical research into leukaemia. In the years since, he has raised hundreds of millions of pounds, helping to fund clinical trial networks, get more drugs into the treatment system and build an infrastructure that allows work to flow and benefits patients.

We need an awful lot more to enable us to fulfill the vision of the blood cancer professors up and down this country because they believe we can beat this in 10 to 15 years eradicate blood cancer. Its such a strong message to get out there and people can see the improvement over the last 15 years that we are getting there.

Collectively, we can beat this.

Listen and subscribe to The Athletics The Moment podcast, including the first episode with Gary Lineker.

(Lead graphic: Sam Richardson)

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More than 500 million people have been diagnosed with COVID-19 since late 2019. Most people who develop COVID-19 have mild disease, but theres compelling evidence that people with certain health conditions like leukemia are at elevated risk of severe disease or death.

A 2021 study presented at the 63rd American Society of Hematology Annual Meeting and Exposition found that people with blood cancer have a 17 percent chance of dying from COVID-19, significantly higher than the general population.

Its less clear if COVID-19 increases your risk of developing leukemia or other blood cancers. Some researchers think its plausible that COVID-19, in combination with other factors, could contribute to cancer development. At this time, the link remains theoretical.

Read on to learn more about how COVID-19 could, in theory, contribute to the development of leukemia.

Some types of blood cancer have been linked to infections. Its not clear if COVID-19 contributes to the development of leukemia, but scientists have found some theoretical links.

Cancer development is usually a consequence of multiple factors that drive genetic mutations in cancer cells. Its plausible that COVID-19 could predispose your body to cancer or accelerate cancer progression.

Most people with COVID-19 recover within 2 to 6 weeks, but some people have symptoms that linger for months. Its thought that the lingering effects result from chronic low grade inflammation triggered by the SARS-CoV-2 virus that causes COVID-19.

Chronic inflammation can cause DNA damage that contributes to the development of cancer. In a study published in April 2021, researchers hypothesized lingering inflammation in people with COVID-19 could increase cancer risk.

The immune response in people with COVID-19 is orchestrated by pro-inflammatory molecules linked to the development of tumors, specifically:

COVID-19 is also associated with other processes known to drive cancer formation such as:

A few case studies have reported people admitted to the hospital with leukemia shortly after developing COVID-19. However, its not clear if COVID-19 played a role or how much of a role it played. Leukemia may have developed coincidentally.

The authors of a 2022 study present a theoretical framework of how COVID-19 could influence the development of blood cancers. According to the researchers, an abnormal immune response to viral infections can indirectly trigger gene mutations that promote leukemia.

The virus that causes COVID-19 can also significantly interact with the renin-angiotensin system, which is suggested to have a role in the development of cancerous blood cells.

In a case study published in 2021, researchers present the case of a 61-year-old man who developed acute myeloid leukemia 40 days after developing COVID-19. The researchers concluded that more studies are needed to assess whether theres an association between COVID-19 and acute leukemia.

In another case study from 2020, researchers presented a man who developed COVID-19 as the first sign of chronic lymphocytic leukemia (CLL). The researchers found that the persons lymphocyte count doubled over 4 weeks, suggesting the viral infection is associated with the replication of B cells, the type of white blood cell that CLL develops in.

Some other types of viral infections have been linked to the development of leukemia.

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, and its rates have been increasing. Growing evidence strongly suggests an abnormal immune response to infections early in life is responsible.

Having a human adult T-cell leukemia virus type 1 infection is linked to the development of T-cell leukemia. This virus is transmitted primarily through bodily fluids. The World Health Organization estimates that 5 to 10 million people have the viral infection.

Some types of infections have been linked to the development of another type of blood cancer called lymphoma. They include:

The FDA has approved the drug remdesivir for adults and some children with COVID-19.

At the time of writing, theres no evidence that remdesivir can cause leukemia.

In a 2021 study, a 6-year-old child with newly diagnosed ALL and COVID-19 was treated with remdesivir and convalescent plasma therapy before starting leukemia treatment.

No adverse events were linked to the therapy, and the researchers concluded this treatment could be considered in people with cancer to accelerate the resolution of the viral infection and to start cancer treatment sooner.

Some researchers have raised concerns that the antiviral drug molnupiravir, which received FDA Emergency Use Authorization on December 23, 2021, could potentially cause cancerous mutations or birth defects. Researchers are continuing to examine these potential adverse effects.

The development of blood cancer is complex. Researchers are continuing to examine whether COVID-19 infection can contribute to the development of leukemia or any other blood cancer. Some researchers have posed a theoretical link, but more research is needed.

None of the vaccines approved for use in the United States interact with your DNA or cause cancer, according to the Centers for Disease Control and Prevention (CDC). Its a myth that mRNA vaccines (Pfizer-BioNTech and Moderna) can cause changes to your DNA.

About 25 percent of blood cancer patients dont produce detectable antibodies after vaccination, according to the Leukemia & Lymphoma Society (LLS). However, the CDC continues to recommend that everyone with cancer still get vaccinated.

LLS experts say vaccination should be combined with other prevention precautions for the best protection.

People with cancer seem to be at a higher risk of severe COVID-19. According to the National Cancer Institute, people with blood cancer may have a higher risk of prolonged infection and death than people with solid tumors.

Researchers are continuing to examine the link between leukemia and COVID-19. Strong evidence suggests that people with leukemia are at an increased risk of developing severe COVID-19.

Some researchers have posed that COVID-19 could contribute to leukemia formation, but as of now, the link remains theoretical. Much more research is needed to understand the connection.

Excerpt from:
Leukemia After COVID-19: Is There a Connection? - Healthline

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