Project Details
Description
ABSTRACT
The therapeutic landscape for Duchenne muscular dystrophy (DMD) has been transformed with the approval
of five new compounds for this disease by the FDA since 2016. Four of the five compounds are antisense
oligonucleotides that induce exon skipping of the dystrophin pre-mRNA, restoring the reading frame for specific
subsets of pathogenic variants. These advances are remarkable, but much work remains to be done.
Approximately two-thirds of the DMD population have pathogenic variants that are not amenable to any of the
currently approved antisense oligonucleotide compounds. Though the life expectancy for DMD is longer than
ever before with a multidisciplinary treatment approach, most affected individuals still lose ambulation during
adolescence and have shortened life expectancies. There have been extensive investigations of cell-based
therapeutic approaches over the past several decades, including some human clinical trials. Our group has
pursued preclinical studies of a stem cell-based approach, which is advantageous due to the potential to
replenish the muscle stem cell pool and enhance long term regeneration of damaged skeletal muscle. With
recent preclinical advances by our team focusing on induced pluripotent stem cell (iPSC)-derived myogenic
precursor cells, the timing is appropriate for a new set of human clinical trials, with the first study to be a Phase
1 evaluation of safety and tolerability of intramuscular injections. Based on extensive successful transplantation
studies in mice, we hypothesize that iPSC-derived myogenic precursor cells will engraft in skeletal muscle
without significant safety concerns. The goal of this planning grant is to prepare the final steps needed to
initiate this Phase 1 clinical trial. The tasks to be completed during the course of this planning period include
formation of the Study Team and commencement of regularly scheduled team meetings; composition and
refinement of a clinical study protocol; composition and refinement of a single site manual of operating
procedures (MOOP) that are compliant with NIAMS requirements; appointment of a data and safety monitoring
board (DSMB) and establish a template for data and safety monitoring reports; submit a single site IRB
protocol; develop a complete set of regulatory documents required for a new IND submission to the FDA; and
preparation of a U01 proposal for the implementation of the Phase 1 clinical trial. By the end of the funding
period, our goal is to have approval from the FDA and the IRB to initiate this study.
Status | Active |
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Effective start/end date | 7/15/22 → 6/30/24 |
Funding
- National Institute of Arthritis and Musculoskeletal and Skin Diseases: $204,600.00
- National Institute of Arthritis and Musculoskeletal and Skin Diseases: $204,600.00
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