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Membrane repair as a therapeutic intervention for treating Becker Muscular Dystrophy

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R42AR083329-01
Agency Tracking Number: R42AR083329
Amount: $295,536.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: NIAMS
Solicitation Number: PA22-178
Solicitation Year: 2022
Award Year: 2023
Award Start Date (Proposal Award Date): 2023-09-21
Award End Date (Contract End Date): 2024-08-31
Small Business Information
1575 Tremont Street
Boston, MA 02120
United States
DUNS: 081066380
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: Yes
Principal Investigator
 (614) 292-5321
Business Contact
Phone: (607) 215-6401
Research Institution
COLUMBUS, OH 43210-1016
United States

 Nonprofit College or University

PROJECT ABSTRACTThe goal of this combined Phase I/II SBIR project is to accomplish key milestones in commercializing a
protein therapeutic for Becker muscular dystrophy (BMD) that will enhance the repair capacity of muscle cell
sarcolemmal membranes compromised by mutations in the dystrophin gene that reduce the expression level
or function of the dystrophin protein. Many mutations in the dystrophin gene result can in BMD while others
result in the more severe Duchenne muscular dystrophy (DMD). Myos Inc. is developing a novel recombinant
construct of the tripartite protein 72/mitsugumin 53 (TRIM72/MG53), an essential regulator of membrane repair
in skeletal and cardiac muscle. It is known that rhMG53 therapy ameliorates disease pathology in a dystrophin
deficient mouse model and models of other muscular dystrophies, strongly suggesting that it may enhance
repair and restoration of muscle function in BMD. However, recent potential toxicity concerns make the original
rhMG53 protein sequence suboptimal for protein therapy. Therefore, we engineered a new version of the
rhMG53 protein for use in treating BMD by optimizing its functional and biochemical properties. This Phase I/II
project will further develop this novel protein by producing the data necessary to support an investigational new
drug (IND) application to the U.S. Food and Drug Administration (FDA) through three specific aims. Aim 1 will
develop Chemistry, Manufacturing, and Control (CMC) protocols for production of this protein. Optimization of
protein production from Chinese Hamster Ovary (CHO) cell cultures will be conducted at a CMO focused on
protein production in CHO cells. We will also conduct stability testing up to 24 months for the protein as part of
the studies in this aim. The deliverables will be a scale-up protocol for production of this protein and generation
of protein for aims 2 and 3. Aim 2 will complete a pre-clinical trial for the efficacy of this protein in treating a
mouse model of BMD. This aim will involve a preclinical efficacy trial for three doses of the protein in a mouse
model of BMD. Randomized cohorts of BMD mice will be treated with for 8-45 weeks and changes in the
dystrophy phenotype will be determined through various measurements of skeletal and cardiac muscle
structure and function. The deliverable for this aim will be to resolve if the protein can effectively treat a rodent
model of BMD. Aim 3 will conduct immunogenicity and toxicity studies for protein in mice. This assessment will
involve toxicity studies, including repeated-dose studies, toxicokinetic assessment, metabolic studies and
immunogenicity assessment, in BALB/c mice. These studies will be conducted at Myos and a CRO with a long
history of conducting such studies. The deliverable here will be completing these studies so the data can be
used to guide regulatory filings. Successful completion of this project will result in sufficient data to prepare an
IND application to the FDA for use in clinical trials for the treatment of BMD.

* Information listed above is at the time of submission. *

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