Disease Focus: Muscular Dystrophy
Engineered iPSC for therapy of limb girdle muscular dystrophy type 2B
Limb girdle muscular dystrophy type 2B (LGMD 2B) is a form of muscular dystrophy that leads to muscle degeneration and disability. In LGMD 2B, a vital muscle protein is mutated, and its absence leads to progressive degeneration of muscles in the body that are needed for mobility. To create a therapy, we will provide a […]
Combination Therapy to Enhance Antisense Mediated Exon Skipping for Duchenne Muscular Dystrophy
Duchenne muscular dystrophy (DMD) is the most common muscular dystrophy and one of the most common fatal genetic disorders. Approximately one in every 3,500 boys worldwide is affected with DMD. Extrapolating from population based studies, there are over 15,000 people currently living with DMD in the US. DMD is a devastating and incurable muscle-wasting disease […]
Interrogating Satellite Cell and Myofiber Defects and Repair in Human DMD using Single Nuclei/Single Cell RNA Sequencing of Muscle Resident Cells
Research Objective We will describe, for the first time, human muscle satellite cell, myofiber and immune cell dynamics due to dystrophin deficiency and AAV gene therapy in human muscle at single nuclei resolution. Impact These studies will elucidate satellite stem cell and myofiber defects in Duchenne and Becker Muscular Dystrophy and determine efficacy, mechanism and […]
Engineering AAV capsids for transduction of neural and muscle stem cells
Research Objective The studies will identify and characterize new gene therapy vectors able to deliver gene editing components to stem cells. to enable treatment of diseases involving both muscle and brain. Impact New AAV capsids that target muscle and neural stem cells will enhance the number of neurological diseases able to be treated with AAV-based […]
Identification and Generation of Long Term Repopulating Human Muscle Stem Cells from Human Pluripotent Stem Cells
Research Objective We will molecularly and functionally define muscle stem cells in human muscle in development, juvenile and adult and develop strategies to generate the most regenerative muscle stem cells from hPSCs. Impact There is no clinically relevant cell endowed with continuous repopulation ability from hPSCs. This work could provide a cell therapy for muscle […]
CRISPR/Cas9 nanoparticle enabled therapy for Duchenne Muscular Dystrophy in muscle stem cells
Research Objective Gene correction of muscle stem cells Impact These studies will develop a gene editing based therapy for one of the most prevalent lethal childhood disorders called Duchenne Muscular Dystrophy. Major Proposed Activities To identify the best MSNP-CRISPR candidates for CRISPR/Cas9 plasmid delivery in vitro to muscle stem cells To identify the best MSNP-STEM […]
Generation of expandable, self-renewing muscle stem cells for Duchenne Muscular Dystrophy
Research Objective The goal of this proposal is to define protocols to generate expandable, self-renewing human muscle stem cells (MuSC) from hiPS cells for Duchenne Muscular Dystrophy disease modeling and therapeutics. Impact The integration of STAT3i with current approaches to derive myogenic cells from hiPS cells would enable the generation of self-renewing MuSC that are […]
Novel Platforms to Enhance In Vivo Delivery of Skeletal Muscle Progenitor Cells from Human Pluripotent Stem Cells
Research Objective Delivery of muscle stem cells presents a major roadblock for therapy. We explore novel approaches to increase the efficiency of delivering and monitoring muscle stem cells derived from hPSCs. Impact Development of enhanced monitoring and delivery platforms will greatly accelerate translational strategies aimed at delivering muscle stem cells for transplantation to patients with […]
Clinical Translation of hESC-derived protein therapy that positively regulates the regenerative capacity of post-natal muscle for treating DM1
Translational Candidate We engineered a human embryonic stem cell-secreted signaling protein into a biologic for treatment of skeletal muscle disorders. Area of Impact Skeletal muscle disorders (including DM1 and sarcopenia) remain major unmet needs that require treatments restoring muscle strength and function. Mechanism of Action Our animal data demonstrate an endocrine stimulation by our biologic […]
Caleb’s Courage: Stem Cell Therapy for Duchenne Muscular Dystrophy
At its July meeting, the CIRM governing Board was honored to hear from Caleb Sizemore, a delightful and courageous young man who was born with Duchenne muscular dystrophy, a fatal genetic disease that causes progressive degeneration and weakening of muscles. Many children with DMD don’t live past their 20s often due to faltering lung and […]