News

Deposits of toxic RNA (red) are seen here
inside muscle cell nuclei (blue) from an individual
with myotonic dystrophy.

Scientists have reversed symptoms of myotonic muscular dystrophy in mice by eliminating a buildup of toxic RNA in muscle cells. The work, carried out by scientists at the University of Rochester Medical Center, Isis Pharmaceuticals Inc. and Genzyme, is published in the August 2 issue of Nature.

After experimental antisense compounds were administered to mice twice a week for four weeks, symptoms of the disease were reduced for up to one year – a significant portion of a mouse's lifespan.

The investigators say that while the work is an encouraging step forward against myotonic dystrophy, one of the most common forms of muscular dystrophy, it's too soon to know whether the approach will work in patients. But they are cautiously optimistic, noting that the compound is extremely effective at reversing the disease – whose genetic underpinnings make it particularly vulnerable to an antisense approach – in a mouse model.

These results give us strong encouragement about the possibility of developing a treatment that could fundamentally alter the disease. It's an important step on a long path, said senior author Charles Thornton, M.D., a neurologist at the University of Rochester Medical Center who has been pursuing new treatments for the disease for more than two decades.

Complex, multi-system diseases like myotonic dystrophy -- the most common adult form of muscular dystrophy -- require physicians and patients to identify which symptoms impact quality of life and, consequently, what treatments should take priority. However, a new study out this month in the journal Neurology reveals that there is often a disconnect between the two groups over which symptoms are more important, a phenomenon that not only impacts care but also the direction of research into new therapies.

People who have the most common type of adult muscular dystrophy also have a higher risk of getting cancer, according to a paper published today in the Journal of the American Medical Association.

The team found that patients who have myotonic muscular dystrophy are at increased risk primarily for four types of cancer: brain, ovary, colon, and the uterine lining known as the endometrium. The team also found a possible increased risk for some other types of cancer, including cancer of the eye, thyroid, pancreas, and other female reproductive organs.

Physicians estimate that approximately 40,000 Americans have myotonic dystrophy, an inherited disease that is marked by progressive muscle weakness. While the course of the disease varies from patient to patient, symptoms can include muscle stiffness, difficulty speaking and swallowing, problems walking, and in some patients, heart problems and cataracts.

Researchers at the University of Rochester Medical Center have found a way to block the genetic flaw at the heart of a common form of muscular dystrophy. The results of the study, which were published today in the journal Science, could pave the way for new therapies that essentially reverse the symptoms of the disease.

The researchers used a synthetic molecule to break up deposits of toxic genetic material and re-establish the cellular activity that is disrupted by the disease. Because scientists believe that potentially all of the symptoms of myotonic dystrophy – the most common form of muscular dystrophy in adults – flow from this single genetic flaw, neutralizing it could potentially restore muscle function in people with the disease.

This study establishes a proof of concept that could be followed to develop a successful treatment for myotonic dystrophy, said URMC neurologist Charles Thornton, M.D., the senior author of the study and co-director of the URMC Wellstone Muscular Dystrophy Cooperative Research Center. It also demonstrates the potential to reverse established symptoms of the disease after they have developed, as opposed to simply preventing them from getting worse.

Most days, neurologist Charles Thornton, M.D., spends some time away from his patients and heads for the laboratory, where he works with mice. It might seem an unlikely action for a doctor ultimately concerned with human health. But his forays in the laboratory have helped Thornton and his team develop a new kind of mouse that may someday help doctors around the world treat patients with myotonic dystrophy, the most common form of muscular dystrophy in adults.