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Translational development of recombinant protein therapeutic for LGMD2B

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41AR081205-01
Agency Tracking Number: R41AR081205
Amount: $259,487.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: NIAMS
Solicitation Number: PA21-262
Solicitation Year: 2021
Award Year: 2022
Award Start Date (Proposal Award Date): 2022-08-01
Award End Date (Contract End Date): 2023-07-31
Small Business Information
Montour Falls, NY 14865-9756
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 ABSTRACTThis Phase I STTR project will accomplish key milestones in commercializing a protein therapeutic for
dysferlinopathies that will enhance the repair capacity of muscle cell membranes compromised by mutations in
the dysferlin gene. The dysferlinopathies include Limb Girdle Muscular Dystrophy Type 2B (LGMD2B), Miyoshi
Myopathy (MMD1) and other, rarer myopathies that all present as adult-onset debilitating muscle diseases
characterized by extensive muscle damage and progressive weakness. All these myopathies arise from
mutations in the gene encoding an essential muscle membrane repair protein, dysferlin. Progress in treatment
of dysferlinopathies has been hampered by the large size of the protein, which complicates gene therapy
approaches, and the complex function of the native dysferlin protein. Myos proposes to develop a treatment for
dysferlinopathies through protein supplementation therapy using a key binding partner of dysferlin, the tripartite
motif protein 72/mitsugumin 53 protein (MG53). MG53 is an essential regulator of membrane repair in skeletal
and cardiac muscle that binds dysferlin and can compensate for the loss of dysferlin in membrane repair. To
provide protein supplementation therapy for dysferlinopathies, we will use recombinant human MG53 (rhMG53)
protein. rhMG53 binds membrane damage sites to enhance membrane repair capacity in cultured cells and
dystrophic animal models when applied outside the cell. Based on these studies, Myos seeks to develop
MyoTRIM, novel engineered version of rhMG53, to treat dysferlinopathy. MyoTRIM is designed to enhance repair
and restore the compromised membrane repair in dysferlinopathy muscle, providing a complementary treatment
approach to other dysferlinopathy therapies in development. The objective of this project is to develop Chemistry,
Manufacturing, and Control (CMC) methods to produce MyoTRIM,protein and to test whether MyoTRIM can
rescue pathology in a dysferlinopathy mouse model using two specific aims. Aim 1 will develop initial CMC
procedures for MyoTRIM. Aim 2 will complete pre-clinical trial for MyoTRIM efficacy in the Bla/J mouse model of
dysferlinopathy. Successful completion of this Phase I project will advance the commercialization MyoTRIM and
provide a significant impact on public health by improving muscle membrane repair to treat muscular dystrophies,
independent of gene or mutation. MyoTRIM will provide a platform technology to target other diseases involving
necrotic cell death.
1PROJECT NARRATIVEThis Phase I STTR project is an important step in advancing a therapeutic that benefits the thousands of
patients with dysferlinopathies, including Limb Girdle Muscular Dystrophy Type 2B (LGMD2B), Miyoshi
Myopathy (MMD1) and other, rarer myopathies that are all characterized by progressive muscle wasting. Myos
will optimize a protein therapeutic to improve muscle cell stability and decrease morbidity for persons with
dysferlinopathies, compared to the current standard of care. This therapeutic would have a significant return for
public health in that it would allow this group of patients to lead lives that are more productive.

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

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