Muscular Dystrophy Collaboration Aims to Correct Muscle Stem Cells’ DNA
January 13, 2020 at 11:00 pm IST
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Harvard University stem cell researchers led by Amy Wagers, PhD, are embarking on a major study of Duchenne muscular dystrophy (DMD). Supported by research funding from Sarepta Therapeutics, under a multi-year collaboration agreement coordinated by Harvard’s Office of Technology Development (OTD), the project aims to use in-vivo genome editing, in mouse models of DMD, to fully and precisely restore the function of the dystrophin protein, which is crucial for proper muscular growth and development. Approaches validated by this work may point the way to an eventual therapeutic strategy to reverse DMD in humans. Duchenne muscular dystrophy is a genetic disease caused by the lack of a protein called dystrophin that normally helps to support the structural integrity of muscle fibers, including those in the heart. Without the dystrophin protein, cells are weaker and degenerate more quickly. Over time, affected individuals — boys, typically, as it is a recessive X-linked disorder — lose their capacity to move independently. Researchers worldwide have pursued a variety of promising approaches — such as cell and gene therapies, small-molecule therapies, and others — to lessen or prevent the disease and improve patients’ quality of life. The strategy pursued by the Wagers Lab at Harvard aims to fully correct the genetic template for dystrophin at its source, in the DNA of stem cells (satellite cells) that create and regenerate muscle cells. Combining cutting-edge CRISPR/Cas9 genome editing technologies with a deep knowledge of stem cell science and regenerative biology, this approach if successful might offer a permanent restoration of muscular function. The new stem-cell approach pursued in collaboration with Sarepta would build on these achievements and use more precise genome editing approaches, in animal models of DMD, to entirely replace genetic mutations in the DMD gene with correctly encoded sequences. The project will also explore alternate delivery methods and strategies to mitigate immune effects of in vivo genome editing. Under the terms of the agreement between Harvard and Sarepta, the company will have the exclusive option to license any arising intellectual property for the purpose of developing products to prevent and treat human disease. As with any research agreement facilitated by OTD, the right of academic and other not-for-profit researchers to use the technology in further scholarly work is preserved.
Sarepta Therapeutics, Inc. is a commercial-stage biopharmaceutical company. The Company is focused on helping patients through the discovery and development of ribonucleic acid (RNA)-targeted therapeutics, gene therapy and other genetic therapeutic modalities for the treatment of rare diseases. It has developed multiple approved products for the treatment of Duchenne muscular dystrophy (Duchenne) and is developing potential therapeutic candidates for a range of diseases and disorders, including Duchenne, Limb-girdle muscular dystrophies (LGMDs) and other neuromuscular and central nervous system (CNS) related disorders. It has developed and commercialized four approved products for the treatment of Duchenne: EXONDYS 51 (eteplirsen), Injection (EXONDYS 51), VYONDYS 53 (golodirsen) Injection (VYONDYS 53), AMONDYS 45 (casimersen) Injection (AMONDYS 45), and ELEVIDYS. Its pipeline includes approximately 40 programs at various stages of discovery, pre-clinical and clinical development.