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

The University of Rochester Medical Center (URMC) has received $8 million from the National Institutes of Health (NIH) to support pioneering research on muscular dystrophy. The grant, which is a renewal of URMC's Paul D. Wellstone Muscular Dystrophy Cooperative Research Center, will fund ongoing work to investigate the genetic mechanisms and progression of this complex multi-system disease, research that has led scientists to the threshold of potential new therapies for myotonic dystrophy.

"The mission of the URMC Wellstone Center is to promote research that leads to effective treatments for muscular dystrophy," said Charles Thornton, M.D., a professor in the URMC Department of Neurology and director of the URMC Wellstone Center. "This new funding will enable us to continue a research program that has been forged from a true partnership between bench scientists, clinical researchers, and patients and their families."

URMC is home to one of six NIH-designated Wellstone Centers in the nation. URMC was selected in the first cycle of funding when the program was launched 16 years ago and is the only Wellstone Center that has been continuously funded since the program's inception. With the current award, URMC has received a total of $29.8 million in NIH funding to study the disease since 2003.

The URMC Wellstone Center focuses on myotonic dystrophy, a disease that can be lethal in infants and adults and is characterized by progressive disability. Researchers at URMC have been studying myotonic dystrophy for more than 30 years and their work has transformed our understanding of the biological mechanisms of the disease. The new funding will support a long-standing collaboration between researchers at the University of Rochester and RNA scientists at the University of Florida.

Approximately 40,000 Americans have myotonic dystrophy, which is one of the most common forms of muscular dystrophy. People with the disease have muscle weakness and prolonged muscle tensing (myotonia), which makes it difficult to relax muscles after use. Eventually many patients have difficulty walking, swallowing, and breathing.

The Center for Neural Development and Disease, led by Harris A. (Handy) Gelbard, M.D., Ph.D., since 2008, will now be the Center for NeuroTherapeutics Discovery, reflecting an increased emphasis on translation and the creation of intellectual property that will lead to new therapies for nervous system disorders.

Gelbard, professor of Neurology, Pediatrics, Neuroscience and Microbiology & Immunology, will continue as director. His research, coupled with the work of Charles Thornton, M.D., professor of Neurology and Neuroscience, and Marc Halterman, M.D., Ph.D., associate professor of Neurology, Neuroscience and Pediatrics, will serve as the anchor of the new center. The trio has a strong track record of grants, publications, and patents, as well as academic and commercial relationships that they are actively pursuing to bring new treatments to the public.

“The Center for NeuroTherapeutics Discovery was developed out of the Center for Neural Development and Disease to create more visibility for academic and commercial partnerships as a necessary bridge for bringing new therapeutics forward,” said Gelbard. “This represents a way to do the best and most cutting edge science possible in a time when the traditional avenues towards funding academic research are changing rapidly.”

The center will bring together many investigators from across the Medical Center and River Campus to identify the mechanisms that lead to various neurological disorders, including HIV-associated neurocognitive disorder (Gelbard lab), myotonic dystrophy (Thornton lab) and stroke (Halterman lab). The center remains committed to its members that investigate the molecular signaling events that lead to nervous system disease during development and aging. Industry partnerships and resources will be sought to fast-track existing therapies or create new molecules that affect these disease mechanisms.

Treatments that harness the immune system to help regenerate damaged cells will be a major focus at the center; the team believes that this approach is broadly applicable to a range of acute and chronic neurodegenerative disorders, such as Parkinson’s disease, multiple sclerosis and Alzheimer’s disease.

University of Rochester Medical Center (URMC) neurologist Charles Thornton, M.D. has received a Javits Neuroscience Investigator Award from the National Institutes of Health to further his research on muscular dystrophy. The unique award provides exceptional researchers with seven years of uninterrupted funding.

The Javits Neuroscience Investigator Award was created by the U.S. Congress in 1983 and is named in honor of former U.S. Senator Jacob Javits (NY), who was the victim of amyotrophic lateral sclerosis, a degenerative neurological disorder commonly known as Lou Gehrig's disease. The $2.3 million grant is administered by the National Institute of Neurological Disorders and Stroke and is given to scientists who have demonstrated exceptional scientific excellence and productivity in their field.

Making progress on treating paralytic diseases is difficult and requires a dedicated team of clinicians and researchers, said Thornton, the Saunders Family Distinguished Professor in Neuromuscular Research. To bring a team together and keep it together over the long run, you need a stable stream of financial support. This award will help us continue our work through a very important stage when new therapies are being tested and others are on the horizon.

Private philanthropic foundations are emerging as a revolutionary source of innovative medical research and development funds. Though the amount of private philanthropic donations as a percentage of medical research spending, is still at a nascent stage, the reality of stagnating federal and state contributions to research and development enterprises is indicative of the future impact that private dollars may have on the field.

Funding for a disease is often scarce when the condition only affects a small portion of the population, or is considered to be less severe than other diseases in its class. Philanthropic medical research donations can target and drive medical advancements in these fields or with these diseases which are relatively neglected.

For example, Michael Goldberg, founding partner at the personal injury law firm Goldberg Weisman Cairo, and his family started the Goldberg Nathan Myotonic Dystrophy Type 2 Fund to encourage medical research into myotonic dystrophy type 2 (a rare genetic disorder characterized by muscular dystrophy).

The Goldberg endowment donated $1.25 million gift to the University of Rochester School of Medicine and Dentistry. The gift will be used to establish a center that will specifically study myotonic dystrophy type 2. Donations from private individuals who have loved ones or family members afflicted with rare genetic conditions are invaluable.

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Richard Moxley

Charles Thornton

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.

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.

A $1.25 million gift from Lilyan (Lil) and Albert (Alfy) Nathan of Florida and Michael and Sherry Goldberg of Chicago will create a new center dedicated to research on myotonic dystrophy type 2 (DM2) at the University of Rochester School of Medicine and Dentistry. The gift will be used to support a new research program that will be led by UR Medicine neurologist Chad Heatwole, M.D.

We are deeply grateful to the Nathan and Goldberg families for their extreme generosity, said Robert Holloway, M.D., M.P.H., the chair of Department of Neurology and the Edward A. and Alma Vollertsen Rykenboer Chair in Neurophysiology. Due to the efforts of Chad Heatwole, Richard Moxley, Charles Thornton, and many others here in Rochester, we believe that new therapies for this disease are on the horizon. This gift will help accelerate these efforts.

Myotonic dystrophy has been characterized as one of the most diverse genetic diseases with a wide range of symptoms ranging from fatigue, muscle stiffness, muscle weakness, cognitive impairment, depression, difficulty sleeping, impaired vision, pain, difficulty swallowing, and gastrointestinal problems. The severity and onset of these symptoms vary from patient to patient.

Dr. Heatwole gave us the first glimmer of hope that someone was actually interested in helping people with this disease, said Michael Goldberg, founding partner of the Chicago firm Goldberg Weisman Cairo. While our family had never made a major donation to a charity or medical institution before, we believed in Dr. Heatwole, the University of Rochester, and in the importance of helping find a cure for DM2 for our son and for the untold number of other people afflicted with this disease.

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.