Myotonic Dystrophy Foundation

The FDA and NIH brought together representatives from patient groups, government, research and industry on September 27-28, 2010, in a meeting titled "Antisense Oligonucleotide Therapies in Neuromuscular Diseases," in Washington DC. Antisense Oligonucleotide’s (AON’s) are short nucleic acid sequences designed for use as small-molecule drugs in the treatment of neuromuscular diseases. This area of research is progressing rapidly in myotonic dystrophy and a number of other diseases, with a growing number of AONs entering pre clinical and clinical development.

Given the growing number of AONs entering clinical development, the FDA and NIH, in collaboration with the research and advocacy communities, are taking a proactive role in developing and promoting regulatory science for the AONs by providing a forum for neuromuscular disease stakeholders to present the 'state-of-the-science' and exchange information on issues relevant to the AONs in relation to four diseases 1) Amyotrophic Lateral Sclerosis (ALS) 2) Duchenne Muscular Dystrophy (DMD) 3) Myotonic Dystrophy (DM) and 4) Spinal Muscular Atrophy (SMA).

In myotonic dystrophy type 1 (DM1), efforts are under way in laboratory studies to develop antisense therapies to block the interactions between expanded RNA in the dystrophia myotonica protein kinase (DMPK) gene and various proteins in the cell, particularly muscle blind (MBNL1), the protein that causes the locking grip phenomenon that is the hallmark of myotonic dystrophy. Abnormally expanded RNA in the DMPK gene is the underlying cause of DM1. There are no clinical trials testing antisense so far in this disease.

Over 120 stakeholders participated in the meeting both live and via webcast of the meeting. Those present at the meeting were researchers, academics, and industry and patient group representatives. The Myotonic Dystrophy Foundation was invited to participate as a patient group representative and our Vice-Chairman, John Brekka attended. He commented: “I think the best development from a patient standpoint was seeing the interaction between all of the stakeholders in this emerging area of research. These developments are exploring the frontier of DNA science and new discoveries are progressing at a more rapid pace Seeing the entire community work together along with government to explore the possible ways of fitting these discoveries into the current regulatory process proves was a highly positive step. While the FDA cannot comment prior to receiving actual drug submissions, they appeared to be clearly welcome opportunities for discussions on how to move forward on the regulatory science in two areas —biochemical and muscle biomarkers and data sharing of AON efforts.”

The goal of the meeting was to allow stakeholders to explore potential pathways forward for the AONs with the eventual goal of creating a sound scientific anchoring for neuromuscular disease clinical development programs. These initial discussions should be seen as first steps in what is likely to be an iterative process intended to lay the ground work for future collaborations. With the leadership of John Porter (NINDA at NIH), Ann Pariser, Associate Director of Rare Diseases at the FDA, Emma Heslop (Treat NMD), and Abby Bronson (CNMC)the initial goal of areas of collaboration and areas for future discussions were established.