MDA Launches Program to Develop Gene Therapies for Ultra-Rare Neuromuscular Diseases

Rare Daily Staff

The Muscular Dystrophy Association said it has launched the MDA Kickstart program for Ultra-Rare Neuromuscular Disease Drug Development in collaboration with UC Davis and a manufacturing partnership with Forge Biologics.

MDA’s Kickstart program will seek to develop strategies and operational solutions to lower barriers and de-risk the translation of gene therapies for ultra-rare neuromuscular diseases.

The Muscular Dystrophy Association said many neuromuscular diseases may be too rare to be commercially attractive for therapy development by drug companies. The new MDA Kickstart Program is an in-house gene therapy program that will partner with academic, corporate, and community groups to move these therapies forward by creating economies of scale and improving valuation of these therapies.

“The MDA Kickstart program will help ensure that patients with ultra-rare forms of neuromuscular disease are not left behind in the era of genetic medicines and can also experience the potential benefits of gene therapies,” said Sharon Hesterlee, chief research officer for MDA.

The selection of the first MDA Kickstart project was guided by external advisors consisting of academic and industry leaders in gene therapy, who reviewed candidate proposals and recommended a genetic condition with high unmet need and a high potential to benefit from a gene therapy approach.

Gene replacement therapy delivered via adeno-associated viruses (AAV) has proven to be a feasible strategy to treat the underlying genetic cause of numerous neuromuscular disorders. While there is expanding interest from industry to support translation studies for AAV-based gene therapies, these have been limited to more common neuromuscular disease subtypes, with minimal commercial interest for indications affecting less than 1,000 people in the United States.

“Currently, an estimated 95 percent of rare disease patients do not have an approved therapy or one in development. We need a medical product paradigm that serves all patients regardless of rarity. The MDA Kickstart program is critical to form an ethical, efficient, and achievable solution to address the existing unmet need for people who are affected by ultra-rare neuromuscular diseases,” said Marina Kolocha, program manager for the MDA Kickstart program.

The first MDA Kickstart project, developed by Ricardo Maselli, professor of Neurology, Clinical Neuroscience, at the University of California, Davis; will focus on the development of a gene therapy for a form of Congenital Myasthenic Syndrome (CMS) caused by mutations in the CHAT gene, which encodes the enzyme choline acetyltransferase.

This enzyme is required for the synthesis of the neurotransmitter acetylcholine, and when it is defective it disrupts the transmission of electrical signals from nerves to muscles, and results in muscle weakness and potentially fatal apnea.

It is estimated that this condition affects about 200 children and adults in the United States and is characterized by muscle weakness and life-threatening episodes of respiratory arrest.

MDA will work with Maselli and team to build a platform for resources and personnel to generate a complete preclinical data package for submission to the U.S. Food and Drug Administration for a formal meeting prior to filing an application to begin human clinical trials.

MDA has partnered with Forge Biologics to provide AAV process and analytical development manufacturing services for the MDA Kickstart program.