Category Archives: Induced Pluripotent Stem Cells

UK animal experiment statistics indicate reluctance to embrace modern tools to advance British labs into the 21st century – Labmate Online

Recently published Home Office statistics [1], have revealed that a high number of dogs, mice, cats, rabbits and other animals some 3.52 million - are still being used in British laboratories despite availability of high-tech and often more human-predictive non-animal approaches.

Humane Society International (HSI) Senior Scientist Dr Lindsay Marshall, who for 12 years managed a laboratory dedicated to animal-free research into respiratory diseases, offers views on some of the reasons that might be preventing a much higher uptake of non-animal techniques that could offer a viable alternative to the use of animal models in research and industry.As a scientist myself, I know all too well the drawbacks of relying on animals to study and treat human disease. The fact is that animal models fail far more often than they succeed, so its hugely frustrating and worrying to see the UK, year after year, failing to move away from outdated animal experiments. Its high time UK research funding bodies stopped squandering British taxpayer money and charitable donations on dead-end research and made a serious investment in human organoids, organs-on-a-chip, computerised systems biology models and other advanced, non-animal technologies that are the true future of modern medical research.Dr Marshall pointed out that in 2010 the Government made a commitment to reduce animals used in scientific research; but almost 10 years after this declaration of intent [2], the UK remains one of the highest lab animal users in Europe. In those same years, non-animal technologies that can produce faster, cheaper and more human-relevant results, have advanced enormously: Computers are much better than animals at predicting possible toxic effects of chemicals and drugs [3] The discovery of induced pluripotent stem cells has helped to remove the ethical barriers to stem cell use [4] Scientists have created human-mimetic systems of almost every organ in the body. There is a human-on-a-chip for drug testing [5], a patient-on-a-chip is not far away [6] and chips have travelled to space to investigate the impact of ageing on the human body [7].

Dr Marshall is not alone in her opinion. A raft of academic reviews from expert scientists in a range of fields reach the same conclusion for conditions as diverse as autism, cardiovascular disease, liver disease, diabetes, and Alzheimers disease [8] and they call for more investment in human-relevant methods.I think that there are many reasons for a reluctance to move away from animals. There is a culture of inertia in research, where animal models have been developed in and are used by a lab, these will be favoured by the researchers and they may see no reason to change or adapt to more relevant, human-focused approaches. Fear of the unknown. Theres an element of familiarity in how to use the animals and understanding the outputs from the animals, that enables persistence of animal models and does not take into account the huge species gap that exists between animals and humans that impacts translation efficiency. Anecdotally, we have heard of more junior researchers being taught and expected to use, the animal methods by their PI, despite a desire to use more human and humane approaches. There is also a requirement to consider the research question in applying non-animal approaches for the first time - there are no simple like-for-like replacements such that a single in vitro assay will stand in for an animal model. We (HSI) do not see this as a reason to continue using the animal models, or to spend scant research resources tweaking existing animal models to create something symptomatically similar to a human condition. Instead, we suggest that researchers look to articulate their research questions in a manner that reflects the novel methodologies emerging and that considers how these methods may be incorporated into a program of research in order to address a specific research question. We believe that framing the question to enable exploitation of the suite of continually developing non-animal methods that are rapidly advancing human relevant science, without compromising safety or discovery, is more likely to translate to much needed treatments and interventions, enables better understanding of human disease. Education and training are required (see below), but at all levels, not just newly qualified researchers.Is the UK government investing enough in research structure support, funding, partnership incentives, graduate/technician education and training?There are some initiatives already- eg the NC3Rs, the Medicines Discovery Catapult - but much of the funding for purely non-animal research is through charities and so is extremely limited and incredibly competitive. The NC3Rs funding for Replacement is combined with initiatives to refine and reduce animal use and it is apparent that this, estimated as around 3% of total research funding in the UK, is not sufficient to encourage the move away from animals. We feel that the Research Councils could use their strategic science roadmaps to help the transitioning of UK life science research to a human biology-based, non-animal paradigm (akin to the US National Academies vision of Toxicity testing in the 21st century or Tox21), with augmented funding for cutting-edge human-relevant technologies and approaches such as human organoids, organs-on-a-chip and elucidation of pathways of human disease and disorders.Education is an important point - there are recognised gaps in training not just for non-animal methods, but ethics and welfare, (see Creating a UK workforce that understands the value and utility of non-animal approaches necessitates revising educational curricula to include modern, relevant, non-animal technologies (e.g. human pathways-based methods). Synchronising educational curricula with high level research objectives is needed to develop a strong, capable workforceappropriately qualified researchers responsive to challenges facing UK science (and consistent with implementation of the Animal (Scientific Procedures) Act). The European Union has just announced their intention to develop online modules for training in non-animal approaches (, but we obviously do not know of the UKs ability to access this after October. Raising awareness is key, but has to go beyond educating budding scientists and tackle that inertia of the established researchers refusing to put down their mice!What incentives do you feel could be more helpful to industry for example, financial (eg through regulatory changes; tax breaks; employment assistance schemes) and through supported research partnership initiatives?Actually, industry are leading the way- in the UK, the number of animals used for regulatory purposes is on the decrease, as the non-animal methods seem to be embraced by industry, perhaps due to the Tox21 initiative which was developed in the US and uses human cell-based assays to develop more efficient approaches in predicting how substances impact human health. Increases in data outputs and efficiency with these approaches have vastly reduced the use of animals in toxicity testing such that only 26% of procedures in the UK in 2018 were for regulatory purposes. One of the barriers to wider uptake of the non-animal approaches for regulatory purposes are the geographical differences in requirements and we at HSI have been calling for global harmonisation for regulatory requirement for some time, and through our work with intergovernmental bodies like the OECD, we are trying to accelerate global adoption of non-animal testing methods.Recently, reviews of the need for animal research facilities in the UK have led to closure of the Wellcome Sanger Institute [9] illustrating the growing recognition within the scientific community that a paradigm shift away from animal use is essential for medical progress. Recognition that fewer animals are required due to a rise in the use of alternative technologies [10] is a step in the right direction, yet the Home Office animal use statistics indicate that there is much more work required to reduce the body count Dr Marshall added.

1. 2018 Home Office statistics: 2. Passini, et al. 2017 Human In Silico Drug Trials Demonstrate Higher Accuracy than Animal Models in Predicting Clinical Pro-Arrhythmic Cardiotoxicity. Front Physiol.8:668.Luechtefeld et al. 2018 Machine learning of toxicological big data enables read-across structure activity relationships (RASAR) outperforming animal test reproducibility. Toxicological Sciences. 165 1, 1 September 2018: 198-2124. https://hesperosinc.com6. Edington et al. (2018) Interconnected Microphysiological Systems for Quantitative Biology and Pharmacology Studies. Sci Rep. 2018 Mar 14;8(1):4530. doi: 10.1038/s41598-018-22749-07. Savoji, et al. 2018 Cardiovascular Disease Models: A Game Changing Paradigm in Drug Discovery and Screening. Biomaterials. 10.1016/j.biomaterials.2018.09.036 Boeckmans et al. 2018. Human-based systems: Mechanistic NASH modelling just around the corner? Pharmacol Res. 134:257-267. 10.1016/j.phrs.2018.06.029 Muotri, A. R. 2016. The Human Model: Changing Focus on Autism Research. Biol Psychiatry. 79;8: 642-9. Bowman, et al. 2018. Future Roadmaps for Precision Medicine Applied to Diabetes: Rising to the Challenge of Heterogeneity. Journal of Diabetes Research. 10.1155/2018/3061620 Clerc, et al. 2016. A look into the future of ALS research. Drug Discov Today. 21;6: 939-499.

Are you working with methods or ideas that could transform the need for animals in research? Are you a producer of technology that reduces the needs for such tests?We would welcome your feedback on the above please email

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UK animal experiment statistics indicate reluctance to embrace modern tools to advance British labs into the 21st century - Labmate Online

Human heart cells change during spaceflight, say scientists in study that could have far-reaching effects on c – MEAWW

Human heart cells are changed by spaceflight but return to mostly normal on Earth, according to a study that examined how the human heart functions in spaceflight. The scientists were surprised as to how quickly human heart muscle cells could adapt to the environment in which they are placed.

The research team examined the cell-level cardiac function and gene expression in human heart cells that were cultured aboard the International Space Station (ISS) for 5.5 weeks. They found that heart muscle cells -- derived from stem cells -- adapted well to their environment during and after spaceflight.

The analysis, says the team, shows that exposure to microgravity altered the expression of thousands of genes, but largely normal patterns of gene expression reappeared within 10 days after returning to Earth.

These findings provide insight into how the human heart functions at the cellular level in spaceflight. This study suggests that the human heart muscle cells are very adaptable to the environment in which they are placed, including microgravity. Microgravity is an environment that is not very well understood in terms of its overall effect on the human body, and studies like this will be able to help shed light on how the cells of the body behave in space," Dr. Joseph C. Wu, Director, Stanford Cardiovascular Institute at Stanford University School of Medicine, told MEA WorldWide (MEAWW).

The researchers explain that human heart muscle cells, like the whole heart, change their functional properties in spaceflight and compensate for the apparent loss of gravity by changing their gene expression patterns at the cellular level.

"This study does not tell us how the heart as a whole changes in microgravity. There are several other types of cells in the heart that were not included in this study. We also do not know how the cells might react if they were exposed to microgravity for a longer period of time. However, these are both things we can test in the future. The results we observed in this study will allow us to focus those future studies on characteristics of the heart muscle cells we know are strongly affected by microgravity," Dr. Wu told MEAWW.

With extended stays aboard the ISS becoming commonplace, there is a need to better understand the effects of microgravity on cardiac function, say experts. Past studies have shown that spaceflight induces physiological changes in cardiac function. Astronauts on space shuttle missions have experienced reduced heart rate, lowered arterial pressure, and increased cardiac output. But to date, most cardiovascular microgravity physiology studies have been conducted either in non-human models or at tissue, organ, or systemic levels, says the team.

"The National Aeronautics and Space Administration [NASA] Twin Study demonstrated that long-term exposure to microgravity reduces mean arterial pressure and increases cardiac output. However, little is known about the role of microgravity in influencing human cardiac function at the cellular level," says the study published in 'Stem Cell Reports'.

Accordingly, the research team used human induced pluripotent stem cells to study the effects of spaceflight on human heart function.

"We studied human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). We generated hiPSC lines from three individuals by reprogramming blood cells and then differentiated them into hiPSC-CMs," says the study.

Dr. Wu explains that human induced pluripotent stem cells (hiPSCs) are stem cells that can be produced from a small sample of blood or skin through a process called "reprogamming".

"These hiPSCs can be then turned into almost any cell type of interest, including beating human heart muscle cells, or cardiomyocytes. Since these hiPSC-derived cardiomyocytes mimic the function of true adult human heart cells, we can use them as a model for how the cells of the human heart respond to microgravity," Dr. Wu told MEAWW.

Beating hiPSC-CMs were launched to the International Space Station aboard a SpaceX spacecraft, as part of a commercial resupply service mission. Simultaneously, ground control hiPSC-CMs were cultured on Earth for comparison.

"Upon return to Earth, space-flown hiPSC-CMs showed normal structure and morphology. However, they did adapt by modifying their beating patterns and calcium recycling patterns," the findings state.

The researchers performed RNA sequencing. "These results showed that 2,635 genes were differentially expressed among flight, post-flight, and ground control samples. A comparison of the samples revealed that hiPSC-CMs adopt a unique gene expression pattern during spaceflight, which reverts to one that is similar to groundside controls upon return to normal gravity," says the study.

The findings, according to the researchers, could provide insight into cellular mechanisms that could benefit astronaut health during long-duration spaceflight, or potentially lay the foundation for new insights into improving heart health on Earth.

"We know that humans can spend months and years in space. Through decades of analyses, we know that the human heart as a whole organ changes its shape, size, and function in spaceflight. These changes are one reason why astronauts must exercise in space for hours every day to keep their heart muscles strong. While our cell-based experiments were able to confirm that changes also occur on the cellular level, we cannot directly translate this to the organ-level without further studies. The changes in our hiPSC-cardiomyocytes are not adverse effects, but rather adaptations to microgravity. The changes reflect how the cells of the human body can quickly adapt to a low gravity environment," Dr. Wu told MEAWW.

The research team now plans to test different treatments on the human heart cells to determine if they can prevent some of the changes the heart cells undergo during spaceflight.

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Human heart cells change during spaceflight, say scientists in study that could have far-reaching effects on c - MEAWW

Space travel may change the human heart – Inverse

Spending time in the microgravity environment aboard the International Space Station appears to alter gene expression in the human heart. The results shed light on what life in space might do to the human body and what happens when that body returns to Earth.

Humans have been venturing out into space for over 50 years now, but very little is known about the toll microgravity might take on the human body. With the age of commercial space travel fast approaching, it is increasingly critical to understand how our bodies adapt to space flight.

Space is our next frontier. In the next 100 years, humans will be traveling through space all the time, says Joseph Wu, Stanford University professor and senior author on the study.

To understand the effect of space travel on our most crucial, blood-pumping organ, in 2016 Wus team sent beating, human-induced pluripotent stem cell-derived cardiomyocytes, a kind of heart muscle cell, to the International Space Station.

The results, published in the journal Stem Cell Reports, show that time in a microgravity environment alters gene expression in the heart muscle cells, but most of these changes revert after the cells are back on Earth.

This is the first study to look at the effects of microgravity on a cellular level, the researchers say.

To create the stem-cell model, the researchers harvested blood cells from three people, none of whom had a history of heart disease. They then reprogrammed the cells to become cardiomyocytes. The cells were sent to the ISS and cultured aboard, staying in the microgravity environment for a total of five and a half weeks before being flown home.

By comparing the cells gene expression in-space, on return and to controls, the researchers found that time in space altered the expression patterns in 2,635 of the cells genes. Most of the altered genes are related to mitochondrial metabolism, the process by which nutrients are converted into energy and used to carry out different functions in cells. Expression patterns looked similar to controls after 10 days back on Earth a possible sign that the body can reverse adaptations to life in space.

We do know that heart muscle cells can adapt. Its hard to tell if these changes are necessarily negative or if they are natural adaptations, says Alexa Wnorowski, a graduate student at Stanford University who was involved in the study.

Its hard for us to come up with a conclusion of what that means. It gives us a future direction to look into, she says.

The team plans to use the data and compare it with both records of physiological changes in astronauts during missions and with symptoms of heart disease in order to get a better sense of these adaptations long-term effects.

The study could also have implications on heart health for those that dont even plan to travel beyond the stars, say the researchers, offering insight into how the environment may affect gene expression in heart cells here on Earth.

Thats one of the hopes for the directions that this type of research might go, Wnorowski tells Inverse. If we figure out that microgravity is able to replicate some of the gene expressions we see in diseases on Earth.

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Space travel may change the human heart - Inverse

Here’s Why Fate Therapeutics Dropped as Much as 19.9% Today – Motley Fool

What happened

Shares of Fate Therapeutics (NASDAQ:FATE) fell nearly 20% today after the company reported third-quarter 2019 operating results and announced it will make six presentations at the upcoming American Society of Hematology (ASH) annual meeting in December. The biopharma disclosed several notable updates and is clearly making progress, but there are certainly a lot of moving parts for investors to understand.

Fate Therapeutics became the first entity to dose a patient with an engineered stem cell-derived cellular medicine in October, began enrolling a higher-dose cohort for a separate drug candidate, announced a new manufacturing facility, and presented several more updates. Therefore, it appears that today's sell-off is an attempt to buy time to digest the sudden increase in complexity, especially considering management decided to hold off important details until the ASH presentations next month.

As of 2:22 p.m. EST, the small-cap stock had settled to a 9.4% loss.

Image source: Getty Images.

Fate Therapeutics was one of the first companies to jump into developing natural killer (NK) cells as therapeutic agents. NK cells offer several notable advantages compared to T cells, the first immune cells to be widely studied in immuno-oncology, including the ability to dose patients multiple times. But they've largely failed to live up to the hype in early clinical studies.

The company is hoping its unique approach can lead to success. Rather than engineering each individual patient's own NK cells, Fate Therapeutics is using a single master cell line -- an induced pluripotent stem cell (iPSC) line -- to engineer cellular medicines that can be given to any individual. That should smooth over manufacturing obstacles, lower costs, and potentially lead to more reproducible outcomes compared to the initial approach used in CAR-T cell therapies.

But there's a lot to digest as the pipeline matures. Fate Therapeutics announced clinical progress for three drug candidates, explained a highly complex phase 1 clinical trial for FT500 in advanced solid tumors, and opened a new manufacturing facility. To the dismay of Wall Street analysts, executives provided few specific details of drug candidates on the third-quarter 2019 earnings conference call and instead chose to wait until the updates at ASH next month.

Investors interested in Fate Therapeutics shouldn't necessarily be discouraged by any recent developments. The company's technology platform ultimately will be judged by clinical results. Given the lack of specific details and a sudden increase in complexity and competition -- including a partnership between Allogene and Notch Therapeutics yesterday and recent fundraising rounds by A2 Biotherapeutics, Nkarta Therapeutics, and Achilles Therapeutics -- Wall Street simply took the "show me" approach. Analysts may get their answers in December.

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Here's Why Fate Therapeutics Dropped as Much as 19.9% Today - Motley Fool

Allogene Therapeutics and Notch Therapeutics Announce Collaboration to Research and Develop Induced Pluripotent Stem Cell (iPSC)-Derived Allogeneic…

Collaboration Includes Exclusive Rights and Targets for Initial Applications in Non-Hodgkin Lymphoma, Leukemia and Multiple Myeloma

Notch to Receive Upfront Payment, Research Funding and an Equity Investment Plus Development and Commercial Milestones and Royalties on Net Sales

SOUTH SAN FRANCISCO, Calif. and TORONTO, Nov. 05, 2019 (GLOBE NEWSWIRE) -- Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage biotechnology company pioneering the development of allogeneic CAR T (AlloCAR T) therapies for cancer, and Notch Therapeutics Inc., an immune cell therapy company creating universally compatible, allogeneic T cell therapies for the treatment of diseases of high unmet need, today announced an exclusive worldwide collaboration and license agreement to research and develop induced pluripotent stem cell (iPSC) AlloCAR therapy products for initial application in non-Hodgkin lymphoma, leukemia and multiple myeloma. Under the partnership, Allogene and Notch will create allogeneic cell therapy candidates from T cells or natural killer (NK) cells using Notchs Engineered Thymic Niche (ETN) platform.

Notch was established in 2018 by Juan Carlos Ziga-Pflcker, Ph.D. and Peter Zandstra, Ph.D., recognized pioneers in iPSC and T cell differentiation technology. Notch is developing a next-generation approach to differentiating mature immune cells from iPSCs. The Notch ETN technology platform offers potential flexibility and scalability for the production of stem cell-derived immune cell therapies. iPSCs may provide renewable starting material for AlloCAR T therapies that could allow for improved efficiency of gene editing, greater scalability of supply, product homogeneity and more streamlined manufacturing.

This collaboration exemplifies Allogenes long-term commitment to advancing the field of cancer treatment as we continue to expand and progress our innovative pipeline of off-the-shelf AlloCAR candidates, said David Chang, M.D., Ph.D., President, CEO and Co-Founder of Allogene Therapeutics. The scientific founders of Notch Therapeutics are among the most respected experts in the field of stem cell biology and its applications to generating T cells and other functional immune cells. We are confident that their technology and expertise, combined with Allogenes leadership in AlloCAR therapies, has the potential to unlock future generations of cell therapy treatments for patients.

Renewable-source, off-the-shelf cell therapies that may produce cells with greater consistency and at industrial scale have long been the dream for people working in this field, said Ulrik Nielsen, Ph.D., Executive Chairman of Notch. We are delighted to spring into the research collaboration for iPSC-based AlloCAR therapies with Allogene, a leader in the allogeneic CAR T field, with the goal of expanding options for patients.

Under the terms of the agreement, Notch will be responsible for preclinical research of next-generation iPSC AlloCAR T cells. Allogene will clinically develop the product candidates and holds exclusive worldwide rights to commercialize resulting products. Allogene will provide to Notch an upfront payment of $10 million. Notch will be eligible to receive up to $7.25 million upon achieving certain agreed research milestones, up to $4.0 million per exclusive target upon achieving certain pre-clinical development milestones, and up to $283 million per exclusive target and cell type upon achieving certain clinical, regulatory and commercial milestones as well as tiered royalties on net sales in the mid to high single digits. In addition to this collaboration and license agreement, Allogene has acquired a 25 percent equity position in Notch and will assume a seat on Notchs Board of Directors.

Master cell banks of genetically modified, induced pluripotent stem cells could provide an inexhaustible source of cell therapies that may improve outcomes and expand applicability to new areas, said Notch Co-Founder Juan Carlos Ziga-Pflcker, Ph.D., a senior scientist at Sunnybrook Research Institute and a Professor and Chair of the Department of Immunology at the University of Toronto.

This work with Allogene may also pave the way for additional off-the-shelf cell therapeutics that are custom-designed to treat other immunity-related diseases such as infectious diseases, autoimmune diseases and aging, said Notch Co-Founder and Chief Scientific Officer Peter Zandstra, Ph.D., a Professor at the University of British Columbia and University of Toronto.

About Notch Therapeutics ( is an immune cell therapy company creating universally compatible, allogeneic (off-the-shelf) T cell therapies for the treatment of diseases of high unmet medical need. Notchs technology platform uses genetically tailored stem cells as a renewable source for creating allogeneic T cell therapies that expand treatment options and deliver safer, consistently manufactured and more cost-effective cell immunotherapies to patients. At the core of Notchs technology is the synthetic Engineered Thymic Niche (ETN) platform, which drives the expansion and differentiation of stem cells in scalable, fully defined, feeder-free and serum-free cultures into T cells that can be genetically tailored for any T cell-based immunotherapeutic application. This technology was invented in the laboratories of Juan-Carlos Ziga-Pflcker, Ph.D. at Sunnybrook Research Institute and Peter Zandstra, Ph.D., FRSC at the University of Toronto. Notch was founded by these two institutions, in conjunction with MaRS Innovation (now Toronto Innovation Acceleration Partners) and the Center for Commercialization of Regenerative Medicine (CCRM) in Toronto.

About Allogene TherapeuticsAllogene Therapeutics, with headquarters inSouth San Francisco, is a clinical-stage biotechnology company pioneering the development of allogeneic chimeric antigen receptor Tcell (AlloCAR T) therapies for cancer. Led by a world-class management team with significantexperience in cell therapy, Allogene is developing a pipeline of off-the-shelf CAR T cell therapycandidates with the goal of delivering readily available cell therapy on-demand, more reliably, and atgreater scale to more patients. For more information, please, and follow @AllogeneTx on Twitter and LinkedIn.

Cautionary Note on Forward-Looking Statements This press release contains forward-looking statements for purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. The press release may, in some cases, use terms such as "predicts," "believes," "potential," "proposed," "continue," "estimates," "anticipates," "expects," "plans," "intends," "may," "could," "might," "will," "should" or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Forward-looking statements include statements regarding intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things: the ability to progress the research collaboration, Notchs ability to develop a next-generation approach to differentiating mature immune cells from iPSCs, the ability to develop and manufacture new therapies from Notch technology, and the potential benefits of Notch technology and AlloCAR T therapy. Various factors may cause differences between Allogenes expectations and actual results as discussed in greater detail in Allogenes filings with theSecurities and Exchange Commission(SEC), including without limitation in its Form 10-Q for the quarter endedJune 30, 2019. Any forward-looking statements that are made in this press release speak only as of the date of this press release. Allogene assumes no obligation to update the forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release.

Allogene Media/Investor Contact:Christine CassianoChief Communications Officer(714)

Notch Media Contact:Mary MoynihanM2Friend

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Allogene Therapeutics and Notch Therapeutics Announce Collaboration to Research and Develop Induced Pluripotent Stem Cell (iPSC)-Derived Allogeneic...

Goldfinch Bio to Present Oral and Poster Presentations at the American Society of Nephrology Kidney Week 2019 Annual Meeting – BioSpace

Nov. 5, 2019 12:00 UTC

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Goldfinch Bio, a U.S.-based, clinical stage biotechnology company focused on discovering and developing precision medicines for the treatment of kidney diseases, today announced it will present one oral and two poster presentations at the American Society of Nephrology (ASN) Kidney Week 2019 Annual Meeting, taking place November 5-10, 2019, in Washington, D.C.

The oral presentation will address the ways in which Goldfinch Bios platform generates induced pluripotent stem cell (iPSC)-derived human podocytes and kidney organoids to enable target validation and preclinical assessment of prospective therapies for kidney disease. The poster presentations will include data on how GFB-887, a sub-type selective, small molecule transient receptor potential canonical 5 (TRPC5) ion channel inhibitor, was effective in reducing proteinuria in animal models of focal segmental glomerulosclerosis (FSGS) and other kidney diseases, as well as data on how Goldfinch Bios proprietary Kidney Genome AtlasTM can be leveraged to unravel molecular mechanisms of kidney diseases.

Details are as follows:

Abstract Title: GFB-887, a Small Molecule Inhibitor of TRPC5, Attenuates Proteinuria in Animal Models of FSGS, Minimal Change Disease, and Diabetic Nephropathy (poster presentation)Session Title: Glomerular Diseases: Podocyte Biology IPresenter: John F. Reilly, Ph.D., Goldfinch BioDate/Time: Thursday, November 7, 2019, from 10:00 a.m. to 12:00 p.m. ETLocation: Exhibit Hall, Walter E. Washington Convention CenterAbstract Number: TH-PO1063

Abstract Title: An iPSC platform for Human Preclinical Evaluation of Kidney Disease Targeting Compounds (oral presentation)Session Title: Glomerular Diseases: Technologies, Mechanisms, and TherapeuticsPresenter: Amy Duyen Westerling-Bui, Ph.D., Goldfinch BioDate/Time: Saturday, November 9, 2019, 5:30 p.m. to 5:42 p.m. ETLocation: 201, Walter E. Washington Convention CenterAbstract Number: SA-OR053

Abstract Title: Unraveling the Genetic Contributions to Kidney Disease with the Kidney Genome Atlas (poster presentation)Session Title: Genetic Diseases of the Kidney - IIIPresenter: Thomas Soare, Ph.D., Goldfinch BioDate/Time: Saturday, November 9, 2019, 10:00 a.m. to 12:00 p.m. ETLocation: Exhibit Hall, Walter E. Washington Convention CenterAbstract Number: SA-PO408

About the Kidney Genome AtlasTM

Goldfinch Bios Kidney Genome Atlas (KGA) is the most comprehensive patient registry to investigate the underlying mechanisms of kidney disease. Through the combination of genomic, transcriptomic and proteomic data with thousands of anonymized clinical patient profiles, Goldfinch Bio is able to conduct unprecedented analyses to elucidate pathways and novel targets for kidney disease.

In May 2019, Goldfinch Bio entered into a strategic collaboration with Gilead Sciences, Inc. to sequence 80,000 diabetic kidney disease (DKD) patients and diabetic controls. Goldfinch Bio received a $55 million upfront payment, including a $5 million equity investment, and a commitment of an additional $54 million to support the development of the KGA platform for DKD. Goldfinch Bio will validate targets and support discovery and development of products to which Gilead will have exclusive option rights in exchange for additional milestone payments.

About GFB-887

GFB-887 is a sub-type selective, small molecule transient receptor potential canonical 5 (TRPC5) ion channel inhibitor in clinical development for the treatment of focal segmental glomerulosclerosis (FSGS), treatment-resistant minimal change disease (TR-MCD) and diabetic nephropathy (DN). The ongoing Phase 1 study is evaluating the safety, tolerability, and pharmacokinetic profile of GFB-887 in healthy volunteers.

TRPC5 is a calcium-permeable ion channel implicated in the pathogenesis of kidney disease. Recent evidence has demonstrated that TRPC5 and Rac1, a critical regulator of cellular motility, form a vicious cycle that drives pathogenic remodeling of the actin cytoskeleton in podocytes. This causes podocyte loss and breach of the filtration barrier, leading to proteinuria, the hallmark of progressive kidney diseases such as FSGS, TR-MCD and DN. Inhibition of TRPC5 offers a potential point of therapeutic intervention to restore podocyte integrity and halt progression of these diseases.

About FSGS, TR-MCD and DN

Focal segmental glomerulosclerosis (FSGS) is a rare kidney disorder and histopathologic diagnosis characterized by scarring of the kidney's filtering units, or glomeruli, leading to proteinuria, an excess of essential proteins spilling into the urine. FSGS is associated with loss of podocytes, terminally differentiated cells of the kidney glomeruli essential for filtration and proper kidney function. Recent research into the genetics of kidney disease has identified over 50 genes associated with FSGS and implicates the podocyte as a central player in the pathogenesis of FSGS. There are currently no FDA-approved treatments available for patients with FSGS.

Similar to FSGS, treatment-resistant minimal change disease (TR-MCD) is a rare kidney disorder characterized by podocyte injury and is an important cause of nephrotic syndrome in children as well as adults. Clinical hallmarks of MCD include rapid onset of edema and weight gain. While MCD may be managed with corticosteroids, a subset of patients fail to respond and are considered treatment-resistant. There are currently no FDA-approved treatments available for patients with TR-MCD.

Diabetic nephropathy (DN) develops in approximately 30 to 40 percent of patients who have diabetes and is a leading cause of end-stage kidney disease, cardiovascular disease and early mortality worldwide. Despite current therapies, the number of people with DN continues to increase, highlighting the need for additional treatments that preserve kidney function.

About Goldfinch Bio

Goldfinch Bio, Inc. is a clinical stage biotechnology company that leverages a genomics-based, precision medicine approach to discovering and developing kidney disease treatments. Its Kidney Genome AtlasTM is a proprietary biology platform that drives candidate discovery, patient selection and biomarker development. The Companys lead candidate, GFB-887, is a transient receptor potential canonical 5 (TRPC5) ion channel inhibitor being evaluated in a Phase 1 clinical trial for the treatment of kidney diseases. Goldfinch Bio is also developing GFB-024, a peripherally-restricted cannabinoid receptor 1 (CB1) monoclonal antibody, for the treatment of rare and metabolic kidney diseases, which it licensed from Takeda Pharmaceutical Company Limited in October 2019. The company expects to submit an IND for GFB-024 in 2H 2020. Goldfinch Bio, headquartered in Cambridge, Massachusetts, was launched in 2016 by Third Rock Ventures and has an established strategic collaboration with Gilead Sciences, Inc. For more information about Goldfinch Bio, visit

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Goldfinch Bio to Present Oral and Poster Presentations at the American Society of Nephrology Kidney Week 2019 Annual Meeting - BioSpace

MD Anderson and Takeda Team Up on Next-Generation Immuno-Oncology Therapeutics – BioSpace

The University of Texas MD Anderson Cancer Center has partnered with Takeda Pharmaceutical on immuno-oncology therapies. Specifically, they announced an exclusive license deal and research agreement to develop cord-blood derived chimeric antigen receptor-directed natural killer (CAR NK)-cell therapies. They say these CAR-NK therapies will be armored with IL-15 to treat B-cell and other cancers.

Under the deal, Takeda will access MD Andersons CAR-NK technology platform and pick up the exclusive rights to develop and commercialize up to four programs. Those programs include a CD19-targeted CAR-NK-cell therapy and a B-cell maturation antigen (BCMA)-targeted CAR-NK therapy. They will collaborate on research to advance the programs.

Our vision is to improve upon existing treatments by developing armored CAR NKs that could be administered off-the-shelf in an outpatient settingenabling more patients to be treated effectively, quickly and with minimal toxicities, said Katy Rezvani, professor of Stem Cell Transplantation and Cellular Therapy at MD Anderson. With their expertise in hematologic malignancies and commitment to developing next-generation cell therapies, Takeda is the ideal collaborator to help our team advance CAR NK-cell therapies to patients in need of treatments.

MD Andersons allogeneic CAR NK technology platform collects umbilical cord blood, isolates NK cells for it, and then engineers those NK cells to express CARs against specific cancer targets. They utilize a retroviral vector to deliver genes to the CAR NK cells, which both improves their effectiveness and fine-tunes them for specific cancer cells. The CD19 CAR makes the cells even more specific for B-cell malignancies, and the IL-15 improves the proliferation and survival of the CAR-NK cells in the body.

Currently approved CAR-T therapies, which essentially means Novartis Kymriah (tisagenlecleucel) and Gilead Sciences Yescarta (axicabtagene ciloleucel), isolate T-cells from the patients blood, which are then engineered to express CARs against the patients specific cancer. The downside to this is that it is time-consuming, taking several weeks. So this approach, which others are also working to develop, would be more of a one-size-fits-all therapy that could be used to treat the patient immediately rather than uniquely engineer the CARs.

MD Anderson and Takeda expect their CD19 CAR NK therapy could be administered in an outpatient setting. There is an ongoing Phase I/IIa trial in patients with relapsed and refractory B-cell cancers. In it, there has been little or no evidence of the severe cytokine release syndrome (CRS) or neurotoxicity associated with Kymriah and Yescartaalthough those companies and the affiliated healthcare practitioners have developed protocols for minimizing those effects.

As well as developing the CAR NK-cell therapies, Takeda and its partners are working to improve the safety, efficacy and accessibility of the first-generation CAR-Ts, including gamma delta CAR-Ts, induced pluripotent stem cell-derived CAR-Ts, CAR-Ts that target solid tumors, and other approaches.

Takeda reportedly hopes to advance five oncology cell therapies into the clinic by the end of fiscal year 2020.

Under the agreement, Takeda will handle development, manufacturing and commercialization of CAR-NK products that come out of the partnership. MD Anderson will receive an undisclosed upfront payment and be eligible for various milestones for each target in addition to tiered royalties on net sales of any products that come out of the deal.

MD Andersons CAR-NK platform is led by Rezvani and supported by the adoptive cell therapy platform, Chronic Lymphocytic Leukemia Moon Shot and B-Cell Lymphoma Moon Shot, which are all part of MD Andersons Moon Shots Program.

MD Andersons CAR-NK platform represents the curative potential of cell therapies, which is why we are establishing the CD19 CAR NK as our lead cell therapy candidate in oncology, said Andy Plump, president of Research and Development at Takeda. We need to work swiftly and with purpose, and as such, we intend to initiate a pivotal study of the CD19 CAR NK in 2021.

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MD Anderson and Takeda Team Up on Next-Generation Immuno-Oncology Therapeutics - BioSpace

Induced Pluripotent Stem Cell Market is expected to witness a strong CAGR of 7.0% from 2018 to 2026 – Zebvo

The healthcare industry has been focusing on excessive research and development in the last couple of decades to ensure that the need to address issues related to the availability of drugs and treatments for certain chronic diseases is effectively met.

Healthcare researchers and scientists at the Li Ka Shing Faculty of Medicine of the Hong Kong University have successfully demonstrated the utilization of human induced pluripotent stem cells or hiPSCs from the skin cells of the patient for testing therapeutic drugs.

The success of this research suggests that scientists have crossed one more hurdle towards using stem cells in precision medicine for the treatment of patients suffering from sporadic hereditary diseases. iPSCs are the new generation approach towards the prevention and treatment of diseases that takes into account patients on an individual basis considering their genetic makeup, lifestyle, and environment. Along with the capacity to transform into different body cell types and same genetic composition of the donors, hiPSCs have surfaced as a promising cell source to screen and test drugs.

In the present research, hiPSC was synthesized from patients suffering from a rare form of hereditary cardiomyopathy owing to the mutations in Lamin A/C related cardiomyopathy in their distinct families. The affected individuals suffer from sudden death, stroke, and heart failure at a very young age. As on date, there is no exact treatment available for this condition. This team in Hong Kong tested a drug named PTC124 to suppress specific genetic mutations in other genetic diseases into the iPSC transformed heart muscle cells. While this technology is being considered as a breakthrough in clinical stem cell research, the team at Hong Kong University is collaborating with drug companies regarding its clinical application.

The unique properties of iPS cells provides extensive potential to several biopharmaceutical applications. iPSCs are also used in toxicology testing, high throughput, disease modeling, and target identification.

This type of stem cell has the potential to transform drug discovery by offering physiologically relevant cells for tool discovery, compound identification, and target validation. A new report by Persistence Market Research (PMR) states that the globalinduced pluripotent stem or iPS cell marketis expected to witness a strong CAGR of 7.0% from 2018 to 2026. In 2017, the market was worth US$ 1,254.0 Mn and is expected to reach US$ 2,299.5 Mn by the end of the forecast period in 2026.

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The quality of the products and lead time can determine the choices while requesting custom solutions at the same time. Companies usually focus on establishing a strong distribution network for enabling products to reach customers from the manufacturing units in a short time period.

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Several leading players have their presence in the global market; however, many specialized products and services are provided by small and regional vendors. By targeting their marketing strategies towards research institutes and small biotechnology companies, these new players have swiftly established their presence in the market.

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Induced Pluripotent Stem Cell Market is expected to witness a strong CAGR of 7.0% from 2018 to 2026 - Zebvo

Can organoids, derived from stem cells, be used in disease treatments? – The Hindu

The story so far: On Monday, October 21, at Neuroscience 2019, the Society for Neurosciences 49th annual meeting, held in Chicago, U.S., two neuroscientists warned the gathering that fellow scientists are perilously close to crossing the ethical red line of growing mini-brains or organoids in the laboratory that can perceive or feel things. In some cases, scientists have already transplanted such lab-grown brain organoid to adult animals. The transplanted organoid had integrated with the animal brain, grown new neuronal connections and responded to light. Similarly, lung organoid transplanted into mice was able to form branching airways and early alveolar structures. These are seen as a step towards potential humanisation of host animals.

Organoids are a group of cells grown in laboratories into three-dimensional, miniature structures that mimic the cell arrangement of a fully-grown organ. They are tiny (typically the size of a pea) organ-like structures that do not achieve all the functional maturity of human organs but often resemble the early stages of a developing tissue. Most organoids contain only a subset of all the cells seen in a real organ, but lack blood vessels to make them fully functional. In the case of brain organoids, scientists have been able to develop neurons and even make specific brain regions such as the cerebral cortex that closely resemble the human brain. The largest brain organoids that have been grown in the laboratory are about 4 mm in diameter.

Organoids are grown in the lab using stem cells that can become any of the specialised cells seen in the human body, or stem cells taken from the organ or adults cells that have been induced to behave like stem cells, scientifically called induced pluripotent stem cells (iPSC). Stem cells are provided with nutrients and other specific molecules to grow and become cells resembling a specific organ. The growing cells are capable of self-organising into cellular structures of a specific organ and can partly replicate complex functions of mature organs physiological processes to regeneration and being in a diseased state.

Organoids of the brain, small intestine, kidney, heart, stomach, eyes, liver, pancreas, prostate, salivary glands, and inner ear to name a few have already been developed in the laboratory.

Since the use of embryonic stem cells to grow organs of interest has been mired in controversy leading to a ban on such research, researchers have turned to generating organoids using stem cells. Researchers have been successful in generating organoids of increasing complexity and diversity. Since the organoids closely resemble mature tissues, it opens up new vistas. These include studying the complex arrangements of cells in three-dimension and their function in detail, and understanding how cells assemble into organs.

Organoids can be used to study the safety and efficacy of new drugs and also test the response of tissues to existing medicines. Organoids will bring precision medicine closer to reality by developing patient-specific treatment strategies by studying which drugs the patient is most sensitive to. Since the use of animals during drug development studies is becoming increasingly difficult, the focus has been on refining, reducing and replacing them. While scientists have been increasingly using human cell lines and other methods, such alternatives have some inherent limitations they cannot mimic the whole organ system. Organoids are a far superior alternative to cell lines.

Organoids offer new opportunities to studying proteins and genes that are critical for the development of an organ. This helps in knowing how a mutation in a specific gene causes a disease or disorder. In a study in Europe using intestinal organoids from six patients with an intestine disorder, it became possible to identify the mutation in a gene that prevented the formation of a healthy intestine. Researchers have used brain organoids to study how the Zika virus affects brain development in the embryo.

Scientists are already using stem cells taken from tumours to grow organoids that are poised to develop cancer. The ability to grow organoids using cancer stem cells allows researchers to study the genes, proteins and signalling pathways that cancer cells use to develop and grow. They are also using healthy organoids to identify and verify the gene mutations that cause cancer.

In an opinion piece in Nature, scientists argued that the largest brain that has been grown in the laboratory is only 4 mm in diameter and contains only 2-3 million cells. In comparison, an adult human brain measures 1,350 cubic centimetres, and has 86 billion neurons and another 86 billion non-neuronal cells and a similar number of non-neuronal cells. The authors argue that organoids do not have sensory inputs and sensory connections from the brain are limited. Isolated regions of the brain cannot communicate with other brain regions or generate motor signals. They wrote: Thus, the possibility of consciousness or other higher-order perceptive properties [such as the ability to feel distress] emerging seems extremely remote.

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Can organoids, derived from stem cells, be used in disease treatments? - The Hindu

University team to seek approval for iPS-based heart treatment trial – The Japan Times

OSAKA A university research team will seek government approval by the end of October to carry out a clinical trial using iPS cells to treat a serious heart condition, Osaka University officials said Wednesday.

The treatment involves transplanting sheets of heart muscle cells, generated from induced pluripotent stem cells that can develop into any type of tissue, to individuals suffering from ischemic heart disease.

The disease is caused by the buildup of plaque in the coronary arteries, which partially or totally blocks blood flow to the heart.

The team, led by Yoshiki Sawa, a professor at Osaka Universitys Department of Cardiovascular Surgery, received approval for a clinical study from the Ministry of Health, Labor and Welfare in May 2018.

But the study was delayed after a powerful earthquake hit western Japan a month later, damaging a research facility where the necessary cells would have been cultivated.

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University team to seek approval for iPS-based heart treatment trial - The Japan Times