Development of MyoDys45-55, a gene editing therapy for Duchenne muscular dystrophy
Grant Award Details
Grant Type:
Grant Number:
TRAN1-12920
Investigator(s):
Disease Focus:
Human Stem Cell Use:
Award Value:
$3,400,000
Status:
Active
Grant Application Details
Application Title:
Development of MyoDys45-55, a gene editing therapy for Duchenne muscular dystrophy
Public Abstract:
Translational Candidate
A gene editing therapy for Duchenne muscular dystrophy that permanently removes a hotspot region of patient mutations to restore dystrophin.
Area of Impact
Duchenne muscular dystrophy (DMD), a fatal muscle wasting disease with no cure.
Mechanism of Action
Our therapy uses CRISPR/Cas9 gene editing to permanently remove a hotspot region of DMD patient mutations, which reframes the gene and restores expression of the dystrophin protein. This approach targets the underlying cause of disease by removing out-of-frame mutations that otherwise would result in a lack of dystrophin and Duchenne disease progression. Thus, restoration of dystrophin by our approach is expected to repair and regenerate damaged muscle in DMD.
Unmet Medical Need
Our therapy is for Duchenne muscular dystrophy, a fatal muscle wasting disease with no cure. There are only a few approved therapies, a corticosteroid (standard of care; slightly improves progression) and exon skipping drugs (only for 8-13% of patients; modestly effective with ~1-3% dystrophin).
Project Objective
Pre-IND meeting
Major Proposed Activities
A gene editing therapy for Duchenne muscular dystrophy that permanently removes a hotspot region of patient mutations to restore dystrophin.
Area of Impact
Duchenne muscular dystrophy (DMD), a fatal muscle wasting disease with no cure.
Mechanism of Action
Our therapy uses CRISPR/Cas9 gene editing to permanently remove a hotspot region of DMD patient mutations, which reframes the gene and restores expression of the dystrophin protein. This approach targets the underlying cause of disease by removing out-of-frame mutations that otherwise would result in a lack of dystrophin and Duchenne disease progression. Thus, restoration of dystrophin by our approach is expected to repair and regenerate damaged muscle in DMD.
Unmet Medical Need
Our therapy is for Duchenne muscular dystrophy, a fatal muscle wasting disease with no cure. There are only a few approved therapies, a corticosteroid (standard of care; slightly improves progression) and exon skipping drugs (only for 8-13% of patients; modestly effective with ~1-3% dystrophin).
Project Objective
Pre-IND meeting
Major Proposed Activities
- Assessment of efficacy, pharmacology and safety in rodent and canine models
- Assessment of off-target editing in human cells
- Development of a potency assay and manufacturing partnership
Statement of Benefit to California:
This proposal will advance preclinical development of our gene editing therapy for Duchenne muscular dystrophy. Duchenne is a devastating muscle wasting disease leading to premature death in the 20-30s. It affects ~1 in 5000 boys worldwide, thus there is a fairly high concentration of Duchenne patients in California. There is currently no cure and only a few approved therapies with limited benefit, thus there is a need for disease modifying therapies that aim to restore dystrophin, like ours.