Muscular Dystrophy Research and Resources at the University of Rochester Medical Center
During the last decade, thanks largely to funding provided by Philip Saunders, scientists and physicians at the University of Rochester Medical Center have made remarkable strides in our understanding of the most common type of muscular dystrophy, called myotonic dystrophy. Charles Thornton, M.D., leads a team that has discovered a previously unknown way that disease can occur in the body. The team found that the disease’s roots lie in the errant buildup of a molecule known as messenger RNA in the nuclei of cells. This “toxic RNA” gets in the way of our normal cellular machinery. The ultimate effect on patients is that a protein crucial for building muscles is lost. Now the team is searching for a way to overcome the defect.
Changing the landscape for boys with Duchenne muscular dystrophy
Rochester doctors have been central to a worldwide research effort to improve treatment for boys affected by Duchenne muscular dystrophy, the most common form of the disease affecting children. The disease causes dramatic muscle weakness. Forty years ago, patients nearly always ended up in a wheelchair by the age of 10 and usually died in their teenage years. Rochester physicians “Rochester scientists Shree Pandya, M.S., D.P.T., Richard Moxley III, M.D., and Emma Ciafaloni, M.D., have been instrumental in showing that aggressive treatment with corticosteroids such as prednisone improves patients’ lives dramatically. Patients on long-term prednisone typically live into their 20s, have improved heart and lung function, and are able to stay mobile for two to five years longer than patients who don’t receive the treatment. Doctors have found that while there are side effects to long-term use of steroids – such as weight gain – for most patients, the benefits far outweigh such side effects. The changes have been so dramatic that Moxley and other physicians are calling attention to other needs of Duchenne patients, such as the need for educational opportunities and friendship, that are becoming more real as patients live longer.
Last year, another team of University of Rochester researchers pinpointed the earliest steps that occur in patients with another form of muscular dystrophy known as FSHD or facioscapulohumeral muscular dystrophy. Scientists discovered that several deleted versions of a gene trigger the remaining copies of that gene to be much more active than usual. That’s because the DNA that codes for the gene is not as tightly coiled or elusive to the body’s molecular machinery as usual when some copies are missing, and so the gene – known as DUX4, which makes a protein harmful to muscle cells – is more active than it should be. The finding by Rabi Tawil, M.D., and colleagues from around the world settled a longstanding question about the roots of the disease and opens up a new therapeutic target for scientists aiming to develop a treatment or cure.
Physicians and other researchers at the University of Rochester Medical Center are beginning a large international study aimed at improving the care of Duchenne muscular dystrophy patients worldwide. Neurologist Robert “Berch” Griggs, M.D., is heading the study of treatments for Duchenne muscular dystrophy. Despite decades of research and provocative findings by Griggs and colleagues about the usefulness of steroids in treating patients, more than two dozen different treatment regimens are currently used by doctors around the world. In the new study, investigators at more than 40 institutions around the world will study the three treatments for the disease most commonly used today. The study, which will include 300 boys ages 4 through 7 throughout North America and Europe, will begin enrolling participants later this year.
The Medical Center is home to one of six Wellstone Muscular Dystrophy Cooperative Research Centers nationwide. Physicians and scientists at the center focus on developing new treatments for myotonic muscular dystrophy. In one set of ongoing studies, doctors are closely monitoring more than 100 patients for three years, studying in detail how the disease progresses. In a second set of studies, Rochester scientists are working with collaborators around the nation, including several pharmaceutical scientists, to test new ways to counter the effects of the genetic flaw that causes the disease. The two studies are deeply linked: To know whether a new treatment is effective, doctors must have be able to understand how the disease normally progresses in patients and to identify ways to tell whether patients are improving. Many of the patients in the study are participating thanks to a 10-year University of Rochester effort to create a registry of patients with the disease, helping doctors and patients interested in taking part in new research efforts to connect. The Wellstone Center, which is funded by the National Institutes of Health and the Muscular Dystrophy Assn., is directed by Richard Moxley III, M.D.
The Muscular Dystrophy Association Clinic at Strong Memorial Hospital provides care for children and adults who have any one of more than 40 types of neuromuscular diseases. The staff includes eight physicians, two nurse practitioners, five clinical technologists, and one representative of the Muscular Dystrophy Assn. Last year more than 1,400 patients from western New York and beyond were cared for at the clinic.