University of Rochester neurologists Richard Moxley, M.D., and Charles Thornton, M.D., have been recognized by the Myotonic Dystrophy Foundation (MDF) with an Outstanding Research Achievement Award. The event took place at the U.S. Capitol earlier this month and honored their contribution to finding new treatments for myotonic dystrophy.
“This award is in recognition of the enduring and transformative collaboration that Drs. Moxley and Thornton have carried out in myotonic dystrophy research and clinical care, and the truly outstanding progress they have made possible in the search for treatments and a cure for the disease,” said Molly White, executive director of MDF.
This recognition follows on the heels of a $7 million grant from the National Institute of Neurological Disorders and Stroke (NINDS) to renew funding for the University’s Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center, a designation that dates back to 2003. The team is also preparing – in collaboration with Isis Pharmaceuticals – to begin testing the first targeted treatment for the disease.
Approximately 40,000 Americans have myotonic dystrophy, a degenerative disease characterized by progressive muscle wasting and weakness. People with myotonic dystrophy have prolonged muscle tensing (myotonia) and are not able to relax certain muscles after use. Eventually many patients have difficulty walking, swallowing, and breathing. The disease can also affect the eyes, the heart, and the brain. Currently there is no medication to halt the progression of the disease.
Researchers at the University of Rochester have been studying the disease for more than 25 years and their efforts are the result of an approach to research and care that stretches from understanding the fundamental biological mechanisms of myotonic dystrophy to the complex nature in which the disease progresses and manifests itself in individual patients.
“Many things had to happen to get us to this point,” said Thornton. “Our approach to translational research is a little different. We used team science to unite several lines of research, all aimed at myotonic dystrophy, in a single program. This includes basic genetics, drug development, preclinical drug testing, and clinical trials. These different activities are typically performed at different locations, but we found that they all work well together and reinforce one another.”
This research has not only required the dedication and focus of a team of scientists and clinicians, but also the tireless commitment and participation of patients and their families.
“Individuals who suffer from myotonic dystrophy and their families have been critical players in this effort,” said Moxley. “Their commitment and altruism has enabled us to learn from their experience and take this information and build an infinitely stronger research program.”
One of the centerpieces of this effort is the National Registry for Myotonic Dystrophy and Facioscapulohumeral Dystrophy, which was established by Moxley, Thornton, Rabi Tawil, M.D., and their colleagues in 2000. This database, which now includes more than 2,200 people with these conditions, has been an invaluable research tool and has enabled researchers across the county to study the disease and recruit participants for clinical trials.
Using the new NINDS funding, the team has also created a new research network – which also includes Ohio State University, Stanford University, the University of Florida, the University of Kansas, and the National Institutes of Health (NIH) Clinical Center – that brings together myotonic researchers to collaborate on new experimental therapies.
These efforts have attracted funding support from a long list of agencies, foundations, and private individuals. Moxley and Thornton particularly single out Phil Saunders, whose early and critical support for their research enabled them generate the initial findings and assemble the scientific team that has served as a foundation for their subsequent efforts.
Over the years, additional support for the team’s research has come from the NIH, the Food and Drug Administration, the Muscular Dystrophy Association, MDF, the Marigold Foundation, Run America Foundation, Isis Pharmaceuticals, and Biogen Idec, among others.
This research has brought scientists to the threshold of a potential new therapy that could reverse the genetic cause of DM1. Partnering with Isis Pharmaceuticals, the Rochester team developed a synthetic molecule – called an antisense oligonucleotide – that mimics a segment of the genetic code. In a study appearing in the journal Nature in 2012, Thornton and his colleagues showed that, when injected into mice with myotonic dystrophy, these molecules improved function. Isis Pharmaceuticals has recently completed Phase 1 testing and will soon advance to testing in people with the disease.