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Archive - Jul 6, 2020

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Exosomes from MSCs Should Be Used in Place of MSCs Themselves for Treatment of “Cytokine Storm” and Severe Pneumonia in COVID-19, Yale Expert Argues; Also, Presence & Role(s) of Billions of Exosomes in Convalescent Plasma Need to Be Considered

In an “Urgent Opinion” pre-print (https://osf.io/zm3ch/) posted online on July 1, 2020, Philip Askenase (https://medicine.yale.edu/news-article/15415/) (https://medicine.yale.edu/profile/philip_askenase/), MD, Professor of Medicine (Clinical Immunology) at the Yale University School of Medicine in the Section of Rheumatology and Clinical Immunology, and former Chief of Allergy & Clinical Immunology at the Yale University School of Medicine, argues that exosomes released from mesenchymal stromal cells (MSCs), should be used instead of MSCs for treatment of the profound clinical “cytokine storm” and severe pneumonia that can occur in COVID-19. He also contends that the presence and role of the billions of exosomes present in convalescent plasma should be considered when using this treatment approach. With regard to the MSC exosomes, Dr. Askenase notes that, although MSCs are increasingly used in the treatment of cytokine storms and pneumonia in COVID-19, many reports in the literature have shown “definitively” that the release of exosomes from in vivo administered MSCs is actually responsible for the beneficial effects associated with the MSCs. In addition, Dr. Askenase noted that exosomes are superior, simpler, and clinically more convenient when compared to their parental MSCs. Furthermore, he pointed out that, in the context of COVID-19, the known tendency of MSCs to aggregate and to cause lung dysfunction might combine with the COVID-19 pneumonia tendencies to exacerbate, rather than help, lung problems associated with COVID-19. In addition, he suggested that the tendency of MSCs to form peripheral vascular micro-aggregates, might synergize with the vascular clots associated with COVID-19 to cause significant central and/or peripheral vascular insufficiency.

Article Examines Epigenetics in Developing Mammalian Embryo; H3K9me3 Histone Marker, Normally Repressive of Gene Expression, Is Non-Repressive in Embryo; Possible New Clue to Cell Reprogramming

Maria-Elena Torres-Padilla (photo), PhD, Director of the Institute of Epigenetics and Stem Cells at Helmholtz Zentrum München, and her colleague Adam Burton, PhD, are doing pioneering work in the field of epigenetics. Together with colleagues, Dr. Torres-Padilla and Dr. Burton published an article on epigenetics in the embryo online on June 29, 2020 in Nature Cell Biology. The article is titled “Heterochromatin Establishment During Early Mammalian Development Is Regulated by Pericentromeric RNA and Characterized By Non-Repressive H3k9me3.” Below, Dr. Torres-Padilla and Dr. Burton responded to some questions on their work. The first question was “Why would we want to reprogram cells?” Dr. Padilla-Lopez answered by saying, “Can you imagine being able to artificially generate cells that can develop into any cell type? That would be really fantastic! We call this ability 'totipotency' and it is the highest level of cellular plasticity. When you think about using healthy cells to replace sick cells, for example in regeneration and replacement therapies, you need to think about how to generate those 'new' healthy cells. For that, you often need to 'reprogram' other cells, that means, to be able to change one cell into the cell type of interest. In nature, cellular reprogramming happens in the early embryo at fertilization. It is a purely epigenetic process since the DNA content of the embryo's cells does not change, only the genes they express. Epigenetics mediates changes in gene expression meaning the way our genes are 'read' from our genetic makeup, which is largely imposed by chromatin.

Regeneron Announces Start of REGN-COV2 Phase 3 COVID-19 Prevention Trial in Collaboration with NIAID; Anti-Viral Antibody Cocktail REGN-COV2 Is Also in Phase 2/3 Treatment Trials Following Positive Phase 1 Safety Review

On July 6, 2020, Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) announced the initiation of late-stage clinical trials evaluating REGN-COV2, Regeneron's investigational double antibody cocktail for the treatment and prevention of COVID-19. A Phase 3 trial will evaluate REGN-COV2's ability to prevent infection among uninfected people who have had close exposure to a COVID-19 patient (such as the patient's housemate), and is being run jointly with the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH). REGN-COV2 has also moved into the Phase 2/3 portion of two adaptive Phase 1/2/3 trials testing the cocktail's ability to treat hospitalized and non-hospitalized (or "ambulatory") patients with COVID-19. This clinical progress follows a positive review from the Independent Data Monitoring Committee of REGN-COV2 Phase 1 safety results in an initial cohort of 30 hospitalized and non-hospitalized patients with COVID-19. The Phase 3 prevention trial is being conducted at approximately 100 sites and is expected to enroll 2,000 patients in the U.S.; the trial will assess SARS-CoV-2 infection status. The two Phase 2/3 treatment trials in hospitalized (estimated enrollment =1,850) and non-hospitalized (estimated enrollment =1,050) patients are planned to be conducted at approximately 150 sites in the U.S., Brazil, Mexico, and Chile, and will evaluate virologic and clinical endpoints, with preliminary data expected later this summer. All trials are adaptively-designed, and the ultimate numbers of patients enrolled will depend on trial progress and insights from Phase 2 studies.