Keio University gets OK for iPS-based heart cell transplant plan – The Japan Times

A health ministry panel on Thursday approved a Keio University clinical research project to transplant heart muscle cells made from induced pluripotent stem (iPS) cells into heart disease patients.

The research will be carried out by a team led by Prof. Keiichi Fukuda for three people between 20 and 74 suffering from dilated cardiomyopathy, which lowers the hearts power to pump blood. The first transplant will be conducted by the end of this year at the earliest.

The team will use iPS cells made by Kyoto University from the blood of a person who has a special immunological type with less risk of rejection.

The team will transform the iPS cells into heart muscle cells and inject about 50 million of them into the heart using a special syringe. Immunosuppressive drugs will be used for about half a year, and the team will spend a year checking to see whether the treatment leads to the development of tumors and irregular heartbeat or whether it restores heart function.

In January, Osaka University conducted the worlds first transplant of heart muscle cells made from iPS cells. The heart muscle cells were made into sheets and pasted on the surface of the patients heart so that a substance they emit can help regenerate the heart muscles. The cells themselves, however, disappear quickly.

Meanwhile, Keio University has confirmed in an experiment on monkeys that cells colonize after a transplant and heart function improves.

The university expects that transplanted cells will colonize over a long period also in the upcoming clinical research project.

According to the team, there are about 25,000 dilated cardiomyopathy patients in Japan.

A startup led by Fukuda is planning a clinical trial aimed at commercializing the iPS-derived cells, hoping they will also be used for the treatment of other cardiac diseases.

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Keio University gets OK for iPS-based heart cell transplant plan - The Japan Times

Stem Cell-Derived Cells Market Forecast to 2025: Global Industry Analysis by Top Players, Types, Key Regions and Applications – The Scarlet

The global Stem Cell-Derived Cells market study presents an all in all compilation of the historical, current and future outlook of the market as well as the factors responsible for such a growth. With SWOT analysis, the business study highlights the strengths, weaknesses, opportunities and threats of each Stem Cell-Derived Cells market player in a comprehensive way. Further, the Stem Cell-Derived Cells market report emphasizes the adoption pattern of the Stem Cell-Derived Cells across various industries.

The Stem Cell-Derived Cells market report examines the operating pattern of each player new product launches, partnerships, and acquisitions has been examined in detail.

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key players in stem cell-derived cells market are focused on generating high-end quality cardiomyocytes as well as hepatocytes that enables end use facilities to easily obtain ready-made iPSC-derived cells. As the stem cell-derived cells market registers a robust growth due to rapid adoption in stem cellderived cells therapy products, there is a relative need for regulatory guidelines that need to be maintained to assist designing of scientifically comprehensive preclinical studies. The stem cell-derived cells obtained from human induced pluripotent stem cells (iPS) are initially dissociated into a single-cell suspension and later frozen in vials. The commercially available stem cell-derived cell kits contain a vial of stem cell-derived cells, a bottle of thawing base and culture base.

The increasing approval for new stem cell-derived cells by the FDA across the globe is projected to propel stem cell-derived cells market revenue growth over the forecast years. With low entry barriers, a rise in number of companies has been registered that specializes in offering high end quality human tissue for research purpose to obtain human induced pluripotent stem cells (iPS) derived cells. The increase in product commercialization activities for stem cell-derived cells by leading manufacturers such as Takara Bio Inc. With the increasing rise in development of stem cell based therapies, the number of stem cell-derived cells under development or due for FDA approval is anticipated to increase, thereby estimating to be the most prominent factor driving the growth of stem cell-derived cells market. However, high costs associated with the development of stem cell-derived cells using complete culture systems is restraining the revenue growth in stem cell-derived cells market.

The global Stem cell-derived cells market is segmented on basis of product type, material type, application type, end user and geographic region:

Segmentation by Product Type

Segmentation by End User

The stem cell-derived cells market is categorized based on product type and end user. Based on product type, the stem cell-derived cells are classified into two major types stem cell-derived cell kits and accessories. Among these stem cell-derived cell kits, stem cell-derived hepatocytes kits are the most preferred stem cell-derived cells product type. On the basis of product type, stem cell-derived cardiomyocytes kits segment is projected to expand its growth at a significant CAGR over the forecast years on the account of more demand from the end use segments. However, the stem cell-derived definitive endoderm cell kits segment is projected to remain the second most lucrative revenue share segment in stem cell-derived cells market. Biotechnology and pharmaceutical companies followed by research and academic institutions is expected to register substantial revenue growth rate during the forecast period.

North America and Europe cumulatively are projected to remain most lucrative regions and register significant market revenue share in global stem cell-derived cells market due to the increased patient pool in the regions with increasing adoption for stem cell based therapies. The launch of new stem cell-derived cells kits and accessories on FDA approval for the U.S. market allows North America to capture significant revenue share in stem cell-derived cells market. Asian countries due to strong funding in research and development are entirely focused on production of stem cell-derived cells thereby aiding South Asian and East Asian countries to grow at a robust CAGR over the forecast period.

Some of the major key manufacturers involved in global stem cell-derived cells market are Takara Bio Inc., Viacyte, Inc. and others.

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Plasma Therapy Market Overview with Detailed Analysis, Competitive landscape, Forecast to 2025 – StartupNG

The Plasma Therapy market research report added by Market Study Report, LLC, is an in-depth analysis of the latest trends persuading the business outlook. The report also offers a concise summary of statistics, market valuation, and profit forecast, along with elucidating paradigms of the evolving competitive environment and business strategies enforced by the behemoths of this industry.

The Plasma Therapy market report provides with a broad perspective of this business space and contains crucial insights such as current and predicted remuneration of the industry, in consort with its size and valuation over the estimated timeframe.

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Genetics of the Tree of Life – Lab Manager Magazine

The African baobab tree (Adansonia digitata) is called the tree of life. Baobab trees can live for more than a thousand years and provide food, livestock fodder, medicinal compounds, and raw materials. Baobab trees are incredibly significant. However, there are growing conservation concerns and until now, a lack of genetic information.

The African baobab tree has 168 chromosomescritical knowledge for further genetic studies, conservation, and improvement for agricultural purposes. The findings were published in the journalScientific Reports. Previous studies estimated that the tree has between 96 and 166 chromosomes.

The African baobab tree has 168 chromosomes in total. USDA researchers used fluorescent probes to see the genetic components of individual chromosomes within the cells.

Islam-Faradi, Sakhanokho & Nelson

"We were able to unequivocally count the chromosomes," says Nurul Faridi, a USDA Forest Service research geneticist who co-led the study with Hamidou Sakhanokho, a USDA Agricultural Research Service research geneticist.

The researchers used fluorescent probes to see the genetic components of individual chromosomes within the cellswhich glow like jewels.

The analysis also revealed that the tree has a massive nucleolus organizer region (NOR). Relative to the main chromosome body, this region appears larger than that of any other plant species. During certain stages of the cell cycle, nucleoli form at the NORs. The nucleoli are essential for ribosome assembly and protein synthesis in eukaryotes and are an important feature that differentiates eukaryotes from prokaryotes.

"These genetic findings are foundational and will make genetic conservation of the African baobab tree more efficient and effective," says Dana Nelson, a coauthor and project leader of the Southern Research Station's genetic unit. "This research is also a precursor for tree breeding programs seeking to improve baobab for silvicultural applications."

- This press release was originally published on theUSDA Forest Service's Southern Research Station website

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Royal Biologics Announces the Acquisition of FIBRINET – PRNewswire

HACKENSACK, N.J., Sept. 1, 2020 /PRNewswire/ --Royal Biologics, an ortho-biologics company specializing in the research and advancement of autologous and live cellular solutions, today announced the completed acquisition of FIBRINET, from Vertical Spine LLC. The acquisition comes as part of Royal Biologics' strategic initiative to add novel technologies to its growing portfolio of autologous and live cellular solutions to support orthopedic and spinal fusion.

The FIBRINET system utilizes a patient's own autologous blood to create a platelet-rich fibrin matrix/membrane (PRFM). During this process, a patient's autologous platelets are harvested first through centrifugation and then combined with a proprietary solution to solidify into a fibrin clot/membrane. PRFM can be used to help augment spinal fusions and provide surgeons a new and novel biologic option. FIBRINET is the first commercialized system that utilizes a non-thrombin solution to create a reproducible platelet-rich fibrin matrix. The use of its proprietary solution to solidify a fibrin membrane provides the unique advantage of creating a biologic reservoir of growth factors and stem cells that can be held and used at the point of care for spinal fusion.

"We are extremely excited to add FIBRINET to our growing portfolio of autologous and live cellular therapies," says Salvatore Leo, Royal Biologics Chief Executive Officer. "FIBRINET'S technology now allows surgeons to harvest a patient's autologous cells and create a unique platelet-rich fibrin membrane-scaffold to be used at the point of care in most spinal fusion procedures. When added to our current product portfolio of autologous and live cellular therapies, we feel that providing each patient an opportunity to harvest their own unique cells for treatment is a superior option in many surgical settings."

FIBRINET has shown promising results and has been adopted into major orthopedic institutions in the United States. Hospitals such as Hospital for Special Surgery, Mount Sinai, NY Presbyterian and Connecticut's Orthopaedic Institute have all adopted FIBRINET into their spine services portfolio of approved products for use.

In a recent European Spine Journalstudy, at a one-year follow-up, FIBRINET demonstrated over a 92.4% radiographic fusion, and there was a significant improvement recorded in VAS scores for both back and leg pain. Compared to baseline figures, the number of patients using opioid analgesics at 12 months decreased by 38%. While the majority (31/50) of patients that participated in the study were retired, 68% of the employed patients were able to return to work.1

"FIBRINET presents itself as a low-cost option to obtain premium, high-quality viable cells from the patient for each fusion procedure," comments Dr. James Yue, Co-Chief and Orthopedic Spine Surgeon at Midstate Medical Center. "During this pandemic, a time when patients are having difficulty receiving operations in major hospital systems, the transition of procedures to ambulatory surgery centers has become even more desired and essential. FIBRINET's low-cost bundle provides surgeons the ability to offer a live viable cell product, point of care in a streamlined and safe environment for spinal fusion."

As part of a national re-launch plan for FIBRINET, Royal Biologics has just launched a new 3D animated moviethat demonstrates the unique features and benefits of FIBRINET's technology. "We wanted to show surgeons, distributors and our peers a new and creative take on Autologous & Live Cellular therapy," comments Leo. "With the recent pandemic and industry environment, we felt it was necessary to help create a unique viewing experience of the FIBRINET system."

FIBRINET comes after two other recent product launches from Royal Biologics in Q1 of 2020. Magnus, a live viable cellular allograft, and Cryo-Cord, a live cellular umbilical cord, were launched in the first quarter of 2020. Both products focus on providing live cellular therapies without the use of traditional toxic cyro-protectants. Both products are new, novel approaches to preserving live cells in a cryo-protected format.

Royal Biologic's FIBRINET is available for U.S. national distribution. Please contact [emailprotected] for more information.

1"Singlecenter, consecutive series study of the use of a novel plateletrich fibrin matrix (PRFM) and betatricalcium phosphate in posterolateral lumbar fusion," European Spine Journal https://doi.org/10.1007/s00586-018-5832-5, July 16, 2018.

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Targeted Approach Considered for the Treatment of Accelerated/Blast Phase MPNs – Targeted Oncology

Standard treatment for accelerated or blast phase myeloproliferative neoplasms (MPNs) consists of hypomethylating agents (HMAs) or intensive induction chemotherapy and transplant. However, newer studies have suggested that accelerated or blast phase MPNs, such as acute myeloid leukemia (AML), can be treated with molecularly driven targeted therapies.

Srdan Verstovsek, MD, explained the current treatment paradigm for patients with accelerated or blast phase MPNs as well as emerging therapies in this setting in a presentation during the Texas Virtual MPN Workshop.1

Current Paradigm and Unmet Needs

Verstovsek, professor in the Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, explained that there are 3 phases of MPNs: chronic, accelerated, and blast (or post-MPN AML), which are determined by the percentage of blasts in the peripheral blood or bone marrow. These phases affect each type of MPN: essential thrombocytopenia (ET), polycythemia vera (PV), and myelofibrosis. In the chronic phase there are less than 10% blasts found in the peripheral blood or bone marrow, and in the blast phase theres 20% or more.

Blast-phase MPNs are associated with a very poor prognosis. It unfortunately has not changed very much over many yearswe have a lot to do, Verstovsek said.

Additionally, those with blast-phase MPNs show limited responses to conventional treatments for AML. In an analysis of 91 patients who developed post-MPN AML, patients who were treated with conventional treatments did not show significant survival differences compared with those who were not treated. The median survival among patients who received induction chemotherapy was 3.9 months compared with 2.1 months for those who did not receive any chemotherapy.2

Stem cell transplant, however, does have a more significant impact on survival following induction chemotherapy. Only patients that achieve complete response [CR] and go for transplant do well, Verstovsek said.

One analysis showed that the rate of overall survival (OS) among patients who did not achieve a CR from induction chemotherapy prior to transplant was 22% compared with 69% among patients who did have a CR (P = .008).3 He said that overall, the chance of achieving a CR with induction chemotherapy is approximately 35% to 40%.4

An alternative to induction chemotherapy is azacitidine, which has shown comparable survival rates to chemotherapy in post-MPN AML. In a study of 73 patients with post-MPN AML, no statistically significant difference was observed in either event-free survival or OS between those treated with chemotherapy or azacitidine. The event-free survival was 4.2 months with induction chemotherapy and 5.8 months with azacitidine (P = .4443) and the median OS was 8.3 and 7.9 months, respectively (P = .9842). Response rates were also similar at 58.8% with chemotherapy and 54.6% with azacitidine.5

The patients that transform from chronic phase MPN to blastic phase MPN actually pass through accelerated phase MPN. That is rather a rule. Its extraordinarily rare that overnight the patient comes from chronic phase to blastic phase, usually you see blasts coming up, Verstovsek said. That is useful because we dont want to wait for patients to transform. If we can follow patients closely, we would be intervening with hypomethylating agents in the accelerated phase.

Research suggests that patients benefit more from HMAs in the accelerated phase than in the blast phase. A retrospective study of patients with high-risk myelofibrosis in the accelerated or blast phase who were treated with decitabine showed that the OS among patients in the blast phase was 6.9 months, but those in the accelerated phase had a median OS of 9.7 months. Among those who responded to decitabine, the median OS was 10.5 months for those in the blast phase and 11.8 months for those in the accelerated phase.6

As ruxolitinib (Jakafi) is standard of care in treating patients with myelofibrosis, the JAK inhibitor has been investigated in clinical trials in combination with HMAs for the treatment of patients with accelerated and blast phase MPNs. When we talk about transformation to accelerated/blastic phase, we are usually talking about [patients with] myelofibrosis transforming, they are in bad physical shape, they have a very big spleen, very big liver, so there is utility perhaps in giving them ruxolitinib, Verstovsek said.

In a phase 1/2 study of ruxolitinib and decitabine in 29 patients with blast phase MPN, treatment with up to 50 mg of ruxolitinib twice daily and 20 mg/m2 of intravenous decitabine for 5 days on a 4 to 6 week schedule led to a response rate of 45%, which included a CR rate of 7%. The median OS for patients who responded to treatment was 9.4 months compared with 6.2 months in those who did not respond.7

We already know that ruxolitinib is not active in preventing progression. On its own its not active in accelerated or blast phasethats already well known, Verstovsek said.

The National Comprehensive Cancer Network (NCCN) guidelines for MPNs now include that ruxolitinib or fedratinib (Inrebic) can be given close to the start of conditioning treatment for the improvement of splenomegaly or disease-related symptoms.8

Overall, Verstovsek suggested starting with HMAs for 2 to 3 cycles because it canbedelivered in the outpatient setting and is not as toxic as chemotherapy, leading to better quality of life for the patient.

Moving Toward a Molecularly Targeted Approach

New medications are being developed for de novo acute myeloid leukemia, so why not use some of them in the setting of post-MPN AML or even in accelerated phase MPN? Verstovsek suggested.

Mutational analyses have shown a significant difference in the mutation frequency found between de novo AML and accelerated or blast phase MPNs. One mutation that is found more often in accelerated or blast phase MPN is IDH1/2, and agents are already available to target these alterations.

Small studies have already shown promise for this approach of treating patients with IDH1/2-mutant accelerated or blast phase MPNs with an IDH1/2 inhibitor. In a small study of 12 patients with IDH1/2-mutant post-MPN AML treated with IDH1/2 inhibitorbased regimens, 3 of 7 patients treated in the frontline setting had a CR and a median duration of response of 17.5+ months was reported. Two patients treated in the frontline and 3 in the relapsed/refractory setting also had stable disease.1

Targeted agentsis the way of the futureidentifying patients based on genetic profile and targeting those mutations for which we have medications, Verstovsek said.

A study has also considered treatment with venetoclax (Venclexta)based combination regimens. The study included 29 patients treated in the frontline or relapsed/refractory setting. Six of the 14 patients treated in the frontline setting achieved a CR or complete response with incomplete hematologic recovery from treatment with the venetoclax regimen and showed a median duration of response of 6 months. However, there was a high degree of infections and mortality in the first 60 days of treatment.1

Additionally, when comparing the venetoclax regimen to other treatment regimens, no survival benefit was found with the use of venetoclax.

Verstovsek summarized that those with targetable mutations, such as IDH1/2 or FLT3 mutations, should receive these targeted treatments, and those with no targetable mutation should receive HMA-based therapy or intensive chemotherapy, and all patients are recommended to undergo allogeneic stem cell transplant if they achieve a complete response and are eligible for transplant.

References:

1. Verstovsek S. Therapy Strategies for Accelerated and Blastic Phase MPN. Presented at: Texas Virtual MPN Workshop; August 27-28, 2020; Virtual.

2. Mesa RA, Li CY, Ketterling RP, Schroeder GS, Knudson RA, Tefferi A. Leukemic transformation in myelofibrosis with myeloid metaplasia: a single-institution experience with 91 cases. Blood. 2005;105(3):973-977. doi:10.1182/blood-2004-07-2864

3. Alchalby H, Zabelina T, Stubig T, et al; Chronic Malignancies Working Party of the European Group for Blood and Marrow Transplantation. Bio Blood Marrow Trasplant. 2014;20(2):279-281. doi:10.1016/j.bbmt.2013.10.027

4. Mascarenhas J. A concise update on risk factors, therapy, and outcome of leukemic transformation of myeloproliferative neoplasms. Clin Lymph Myel Leuk. 2016;16(suppl):S124-S129. doi:10.1016/j.clml.2016.02.016

5. Venton G, Courtier F, Charbonnier A, et al. Impact of gene mutations on treatment response and prognosis of acute myeloid leukemia secondary to myeloproliferative neoplasms. Am J Hematol. 2018;93(3):330-338. doi:10.1002/ajh.24973

6. Badar T, Kantarjian HM, Ravandi F, et al. Therapeutic benefit of decitabine, a hypomethylating agent, in patients with high-risk primary myelofibrosis and myeloproliferative neoplasm in accelerated or blastic/acute myeloid leukemia phase. Leuk Res. 2015;39(9):950-956. doi:10.1016/j.leukres.2015.06.001

7. Bose P, Verstovsek S, Cortes JE, et al. A phase 1/2 study of ruxolitinib and decitabine in patients with post-myeloproliferative neoplasm acute myeloid leukemia. Leukemia. 2020;34(9):2489-2492. doi:10.1038/s41375-020-0778-0

8. NCCN Clinical Practice Guidelines in Oncology. Myeloproliferative neoplasms, version 1.2020. Accessed August 28, 2020. https://www.nccn.org/professionals/physician_gls/pdf/mpn.pdf

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Targeted Approach Considered for the Treatment of Accelerated/Blast Phase MPNs - Targeted Oncology

Novel Targets Outside of JAK Inhibition Inching into Myelofibrosis Treatment Landscape – Targeted Oncology

Experts in myeloproliferative neoplasms find janus kinase (JAK) inhibitors to be particularly important to the armamentarium for the treatment of myelofibrosis (MF). With only 2 FDA-approved agents, fedratinib (Inrebic) and ruxolitinib (Jakafi), and the inevitability that not all patients will derive benefit, and some will develop resistance, the option of moving beyond JAK inhibition is widely discussed.

During a presentation at the 1st annual Texas Virtual MPN Workshop, Naveen Pemmaraju, MD, associate professor, Department of Leukemia, University of Texas MD Anderson Cancer Center discussed the novel therapies beyond JAK inhibitors that are making their way into the treatment landscape of MF.1

Currently, novel agents are showing promise in phase 3 clinical trials, include pacritinib (SB1518) in the phase 3 PACIFICA study (NCT03165734), momelitinib (formerly GS-0387) is being evaluated in the phase III MOMENTUM study (NCT04173494), and fedratinib, although approved in the frontline setting, is now being evaluated as second-line treatment.

Modern JAK Inhibition Combinations

Ruxolitinib remains the standard-of-care treatment for patients with MF, even with the emergence of novel therapies, Pemmaraju noted. To improve upon outcomes in the patient population, ruxolitinib is now being rechallenged in patients or combined with other drugs. One study for which data were published in a 2018 issue of Blood, explored the addition of ruxolitinib to the chemotherapy agent azacitidineazacitidine (Vidaza).

The phase 2 study of ruxolitinib plus azacitidineazacitidine included 44 patients with MF whose median age was 66 years (range, 48-87 years). At baseline, 36 patients (82%) had intermediate-2 (int-2)/high IPSS score, 29 patients (66%) had splenomegaly, and 24 patients (55%) were positive for a JAK V61F mutation.

Thirty-nine patients were evaluable for response. The median follow-up time was 20.4 months (range, 0.5-3.7). The results showed objective response in 33 patients (72%) which included 2 partial responses and clinical improvement in 31 patients. The median time to response was 1.8 months (range, 0.7-19 months). In addition, the combination of ruxolitinib and azacitidine led to spleen response in 21 (61%) of the 34 patients who had splenomegaly > 5cm. In 3 other patients whose splenomegaly was 5 to 10 cm at baseline, there was a 50% reduction in spleen size following treatment with the ruxolitinib combination.

Another phase 2 clinical trial evaluated treatment with ruxolitinib plus navitoclax in patients with JAK2-resistant MF (NCT03373877). The combination demonstrated clinical activity in these patients, according to findings presented at the 2019 American Society of Hematology Annual Meeting. In 30% of the study population, there was a spleen volume response of greater than 35%. In addition, there was a 65% reduction in symptoms and 35% of patients had a reduction in total symptom score (TTS) of more than 50%.

Pemmeraju also noted an ongoing phase 1b study of ruxolitinib plus PU-H71 in patients with MF and polycythemia vera (PV, NCT03373877). In addition, the add-on strategy is being explored with lenalidomide (Revlimid), thalidomide (Thalomid), pracinostat, CPI-0610, sotatercept (ACE-011) plus luspatercept (Reblozyl), as well as in combination with a PI3k (phosphoinositide 3-kinase) inhibitors and interferon inhibitors.

Possible Modern JAK Inhibition Strategies

Targeting JAK is no longer the only strategy available for MF in 2020, Pemmaraju explained. Research has shown that there are possibilities for targeting apoptosis and cell death pathways, telomerase, hematopoietic stem cell, and microenvironments, the TP53 pathway, and targeting fibrosis, cytokines, epigenetics, and other pathways.

In relation to targeting apoptosis and cell death pathways, the phase 2 study of single-agent LCL-161 (NCT02098161) investigated 50 patients with primarily relapsed/refractory MF. A phase 2 open-label study of navitoclax alone or in combination with ruxolitinib (NCT03222609) is also testing out this strategy. The telomerase inhibitor, imtelestat, was also studied in this patient population in phase 2 study (NCT02426086).

There are 2 ongoing trials (NCT02268253 and NCT03373877) investigating the targeting of hematopoietic stem cell/microenvironment. One study is also assessing the targeting of the TP53 pathway in patients with MPNs as well as post-MPN acute myeloid leukemia (AML). Other trials that Pemmaraju mentioned that are investigating fibrosis, cytokines, epigenetics, and other pathways as targets include the phase 2 study of pentraxin (PRM-151, NCT01981850), as well as the studies of sotatercept/luspatercept, alisertib (MLN8237), CPI-0610, and PSD1 inhibition.

Promise of MF Treatment Beyond JAK Inhibition

Multiple treatment strategies have shown positive results in clinical trials as treatment of patients with high-risk MF, Pemmaraju shared. First, he shared results of the phase 1/2 trial of a novel CD123-directed therapy, which was designed to address the CD123 expression seen in many myeloid malignancies, including MF.

Tagraxofusp

In the phase 1/2 trial of tagraxofusp, 32 patients were included in the safety analysis for the study, and more than 10% experienced treatment-related adverse events (TRAEs). The most common TRAEs of any grade were hypoalbuminemia (25%), headache (16%), alanine aminotransferase increased (16%), anemia (14%), and thrombocytopenia (14%).

At baseline, 18 patients had splenomegaly 5 cm, and of those patients, 10 (56%) had spleen reductions. Additionally, 2 patients had spleen reductions of greater than 50%. Among patients with thrombocytopenia and platelet counts <100 109/L 8 patients (62%) had spleen size reduction as did 4 patients (57%) with thrombocytopenia and platelets < 50 109/L. Subjects with monocytosis whose monocytes were 1 109/L. In addition, 46% of the 24 patients evaluated to efficacy had a reduction in their TTS.

In terms of survival, the median OS observed was 30.5 months at a median follow-up time of 27 months (range, 0.6-50.3 months).

According to Pemmaraju, the subsets of patients with MF who had thrombocytopenia, monocytosis, or accelerated phase disease are areas of ongoing research.

LCL161

LCL161 was the second agent Pemmaraju noted as a potential new treatment for high-risk MF. The agent was assessed in a phase 2 clinical trial which was launched to address the unfavorable survival outcomes in the patient population. In addition, no JAK inhibitors are approved by the FDA as treatment of this particular group of patients with MF.

In 50 patients, the objective response rate was 30%, leading clinical improvements in 11 patients with symptoms, 6 patients with anemia, and 1 pain with splenomegaly. Additionally, 1 patient achieved a cytogenetic remission.

The survival data show that 34 patients (68%) were still alive at data cutoff. The median duration of response was 1.4 months (95% CI, 0.9-9.1 months). There was also a number of longer-term responses (n = 8) who experienced a response for 1 year or more. At data cutoff, long-term responses were ongoing in 4 patients. The median OS was not reached in the study.

Based on these data, Pemmaraju stated that LCL161 may be a viable option for older patients, those who failed prior JAK inhibitors, and those with thrombocytopenia that limit entry into clinical trials.

Luspatercept

Data presented previously at the 2018 American Society of Hematology (ASH) Annual Meeting showed that a phase 2 study of luspatercept was positive for its primary and secondary end points of transfusion independence.1,2

In a cohort of 22 patients who were not receiving ruxolitinib and had no red blood cell transfusion for 12 consecutive weeks, 14% achieved the primary end point and 18% achieved the secondary end point. In a separate cohort of 21 patients who were not receiving ruxolitinib and had been transfusion dependent for 12 consecutive weeks, 10% were positive for the primary end point and 38% were positive for the secondary end point. In the cohort of 14 patients who were receiving a stable dose of ruxolitinib and were transfusion independent of 12 consecutive weeks, 21% reached the primary end point and 64% achieved the secondary end point. Finally, in the cohort of 19 patients who received a stable dose of ruxolitinib but were transfusion-dependent for 12 consecutive weeks, 32% achieved the primary end point and 53% achieved the secondary end point.

CPI-0610

Preliminary results for CPI-0610 were also presented at ASH in 2019. In the phase 2 study CPI-0610 was combined with ruxolitinib in treatment-nave patients with MF.1,3

Compared with baseline measurements, an 80% SVR35 (spleen volume reduction) response was observed at week 12, demonstrating a median change from baseline of -49.7% (range, -80.8% to -17.0%). Responses were also observed in high-risk patients including 86.7% of those with DIPSS Dynamic Prognostic Scoring System (DIPPS) int-2, 80% with hemoglobin < 10g/dL, and 53.3% of patients with high molecular risk (HMR) positivity.

In terms of total symptom score (TSS) improvement, it was observed that 71.4% of patients had a TSS response at week 12, and this included the treatment nave population with an improvement of 45.9%.

Navitoclax

In another phase 2 study, navitoclax with or without ruxolitinib demonstrated promise in patients with primary of secondary MF. The drug specifically helped patients overcome resistance to ruxolitinib which resulted in splenomegaly improvement.1,4

Out of 30 patients assessed, SVR35 at week 24 was 43% in 13 patients and 30% in 9 patients. In addition, resolutions of palpable splenomegaly were observed in 53% of patients. Twenty-five percent of patients also demonstrated reductions in bone marrow fibrosis per local assessment.

Imetelstat

A randomized phase 2 study of imetelstat as treatment of patients with intermediate-2 or high-risk MF who were relapsed or refractory to JAK inhibition induced responses and a survival benefit.1,5

In a pool of 107 patients, 6 patients (10%) had 35% SVR at week 24 and 23 patients (37%) had a 10% SVR at week 24.

Imetelstat also achieved a median OS of 19.9 months (95% CI, 17.1-not evaluable [NE]) when administered at a dose of 4.7 mg.kg and the median OS climbed to 29.9 months (95% CI, 22.8-NE) when Imetelstat was administered at 9.4 mg/kg.

Pemmaraju noted that a review of the existing and ongoing research on targeting beyond JAK inhibition in patients with MF was recently published in Current Hematologic Malignancy Reports. The paper states that because of the different mechanisms of action other the novel therapies in MPNs, they can improve outcomes in the field when use alone or in combination with ruxolitinib.6

References:

1. Pemmaraju N, et al. Novel Targeted Therapies Beyond JAK Inhibitors. Presented at: Texas Virtual MPN Workshop; August 2728, 2020; Virtual.

2. Gerds AT, Vannucchi AM, Passamonti F, et al. A Phase 2 Study of Luspatercept in Patients with Myelofibrosis-Associated Anemia. Blood. 2019;34(supplement_1):557. doi: 10.1182/blood-2019-122546

3. Mascarenhas J, Kremyanskaya M, Hoffman R, et al. MANIFEST, a Phase 2 Study of CPI-0610, a bromodomain and extraterminal domain inhibitor (beti), as monotherapy or "add-on" to ruxolitinib, in patients with refractory or intolerant advanced myelofibrosis. Blood. 2019; 134 (Supplement_1): 670. doi: /10.1182/blood-2019-127119

4. Harrison CN, Garcia JS, Mesa RS, et al. Results from a phase 2 study of navitoclax in combination with ruxolitinib in patients with primary or secondary myelofibrosis. Blood. 2019;134(supplement_1):671. doi: 10.1182/blood-2019-130158

5. Mascarenhas J, Komrokji RS, Cavo M, et al. Imetelstat is effective treatment for patients with intermediate-2 or high-risk myelofibrosis who have relapsed on or are refractory to janus kinase inhibitor therapy: results of a phase 2 randomized study of two dose levels. Blood. 2018;132(supplement_1):685. doi: 10.1182/blood-2018-99-115163

6. Economides, M.P., Verstovsek, S. & Pemmaraju, N. Novel therapies in myeloproliferative neoplasms (mpn): beyond jak inhibitors.Curr Hematol Malig Rep.2019;14,460468. doi: 10.1007/s11899-019-00538-4

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Novel Targets Outside of JAK Inhibition Inching into Myelofibrosis Treatment Landscape - Targeted Oncology

Parents plea for stem cell help to save life of daughter with rare blood disorder – Mirror Online

The parents of a girl battling a deadly blood disorder are begging people to join the stem cell donor register to save her life after her only match in the world pulled out at the last minute.

Evie Hodgson, eight, who suffers from aplastic anaemia, was due to have a bone marrow transplant this month but her donor backed out at the last possible moment.

Her mum, Tina, says the chances of finding another donor are so slim that doctors are now planning a different course of treatment. But, in future, a stem call transplant is Evies best hope of being cured.

The schoolgirl, from Whitby, North Yorks, was first taken to hospital with a rash and was diagnosed with aplastic anaemia in May.

After a global donor search was launched, a 10/10 match was found and the anonymous donor agreed to the procedure. In preparation, Evie had to have dental work and one of her ovaries was removed. But on August 14 the donor pulled out.

Tina, 37, who works at RAF Flyingdales, in Pickering, North Yorks, said: We were devastated, it was a huge blow. We have no idea why the donor changed their mind. Evie has already been through so much. She thought she had a donor and now she doesnt.

The donor pulling out is quite hard-hitting, but we want to raise awareness of the stem cell register. Its so easy to be a donor. Its just like giving blood, but you could save a childs life. Its so easy to join but only 1% of the UK population is registered.

Evie said: I need this transplant to save my life. Please sign the register to help.

Tina added: The condition Evie has is life-threatening. She wont survive without a transplant. We are desperately appealing for people to sign the stem cell register.

Evie was diagnosed with the condition after she developed a pin-prick rash on her back, which didnt fade. Tests revealed she had low blood platelet levels and she was told she needed a bone marrow transplant.

Aplastic anaemia is a rare life-threatening condition where the bone marrow fails to produce enough blood cells. Around 100-150 people are diagnosed in the UK each year.

Treatment can include immunosuppressants, chemotherapy, blood transfusions, or blood and bone marrow transplants.

Neither Tina, dad Andy, 49, or brother William, five, were a match and so an international search was launched.

Tina said: Our world crumbled when Evie was diagnosed. Evie knew shed need chemotherapy. She donated her hair to The Little Princess Trust, after making friends with poorly children who have lost all their hair.

Evie will be treated with immunosuppressants while the search for a donor continues.

Blood cancer charity Anthony Nolan is looking for stem cell donors between the ages of 16-30.

Research shows that younger donors result in better outcomes for patients.

To find out how to donate click here.

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Parents plea for stem cell help to save life of daughter with rare blood disorder - Mirror Online

Stem Cell Therapy Market Scope and Opportunities Analysis 2017 2025 – StartupNG

Global Stem Cell Therapy Market: Overview

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

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

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Global Stem Cell Therapy Market: Key Trends

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

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

Global Stem Cell Therapy Market: Market Potential

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

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

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

The regional analysis covers:

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Global Stem Cell Therapy Market: Regional Outlook

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

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

Global Stem Cell Therapy Market: Competitive Analysis

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

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

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Breath to the rescue: COVID-19 is offered to be treated with cellular inhalation – Pledge Times

Scientists from China have proposed treating severe coronavirus pneumonia using cellular technologies. They plan to use exosomes stem cell secretion products as an active component. Experimental studies have shown that their use significantly reduces pneumonia. This technique is safer than injecting the stem cells themselves into the patient, since there is no risk of mutations and cancer development. Another advantage of such therapy is the ability to store drugs for several weeks or even months, which ensures their safe transportation and delayed use. Russian experts believe that the technique looks promising.

Despite the fact that effective methods of treating patients with severe coronavirus infection have already been worked out, many people, especially the elderly and those with poor health, are still at high risk of dying from pneumonia. Therefore, it is imperative to find a safe and effective therapeutic approach for patients with COVID-19 complicated by acute respiratory distress. In this regard, many research teams are turning their attention to the prospect of using human stem cells.

Scientists at the Shanghai Public Health Clinical Center and Jinyintan Hospital in Wuhan plan to launch a pilot study inhalations with stem cell waste products. We are talking about exosomes bubble-like small particles that release all types of cells into the surrounding fluids. They are needed for the intercellular transfer of various proteins or microRNAs. Such exosomes are also secreted by mesenchymal stem cells, which are proposed to be used in the treatment of severe coronavirus pneumonia.

Photo: REUTERS / Richard Chung

Experimental studies have shown that their use significantly reduces lung inflammation and pathological disorders resulting from various types of lung damage, said in the text of the description of the clinical study. At the same time, scientists note that the intravenous administration of living stem cells (not exosomes), which is also now being studied by various scientific teams, can carry the risks of mutations and the development of cancer. What is not observed in the treatment of cells sprayed in an aerosol.

Another advantage of the proposed technique is the possibility of storing such drugs for several weeks and months, which ensures their safe transportation and delayed therapeutic use. As stated in the document, it is planned to recruit 30 participants for the first stage. It is assumed that each will undergo five inhalation procedures.

Mesenchymal stem cells (MSCs) interact with the innate immune system and can have both anti-inflammatory and pro-inflammatory activity. The type of activity is determined by the source of MSC production, surface markers, the profile of secreted cytokines (proteins secreted by immune cells. Izvestia) and other factors, the acting newspaper told the newspaper. Andrei Vasin, director of the Institute of Biomedical Systems and Biotechnology, Peter the Great St. Petersburg Polytechnic University (the university is a participant of the 5-100 education competitiveness project).

Since the acute respiratory distress syndrome (ARDS) in COVID-19 is believed to be the result of an imbalance of cytokines and other molecules involved in inflammatory responses, it seems reasonable to use approaches to mitigate these responses. A number of studies have been carried out, which suggested the effectiveness of MSCs for the treatment of ARDS, explained Andrei Vasin. Since some of the functions are realized due to the molecules secreted by these cells, it was proposed to use not them, but exosomes containing these molecules.

Scientists have shown that in some cases the use of exosomes gave the same results as the use of MSCs. Therefore, the stem cells themselves do not need to be injected into the patient. This is the approach that the Chinese researchers decided to use in this clinical study, noted Andrey Vasin. And the very possibility of aerosol administration of the drug potentially has a number of advantages from the point of view of the safety profile and the direction of delivery to the pathology site.

Photo: TASS / Zuma / Xinhua

In general, since the beginning of this year, about two dozen studies have been organized around the world using cellular products, Alexey Lyundup, Executive Director of the Association of BMCP (Biomedical Cell Products) Manufacturers, told Izvestia. Moreover, the sources of cells can be different.

The method proposed by Chinese experts is supposed to use exosomes of adipose tissue MSCs, the expert emphasized. Research continues, the idea itself is promising.

According to the specialist, such exosomes from MSCs contain cytokines and growth factors (natural compounds that can stimulate the production of living cells), signal lipids (substances that transmit signals inside the cell) and other substances necessary to relieve inflammation. However, it is worth waiting for evidence of the safety and effectiveness of their use in preclinical studies. And only then begin clinical trials declared by Chinese scientists.

We have sufficient grounds to believe that mesenchymal stem cells (as well as exosomes with similar properties. Izvestia) extinguish the cytokine storm, said Stanislav Otstavnov, deputy head of the laboratory for analysis of population health indicators and digitalization of healthcare at MIPT. I assess the proposed methodology in China as promising, but clinical trials will tell about the effectiveness and safety. In theory, cell therapy should also help in the regeneration of damaged lung areas, but there is little specific information in official sources on this matter. But the decrease in the immune response has been confirmed.

The experts emphasize that, in general, the available data on the use of exosomes in patients with COVID-19 looks interesting and this approach may be promising. However, so far unanswered questions remain related to the dose of such drugs, the route and frequency of administration, recipient groups, interaction with other treatment methods, and so on. Therefore, research in this direction must be continued.

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Breath to the rescue: COVID-19 is offered to be treated with cellular inhalation - Pledge Times