The Rochester center, which will focus on three uncommon neurological disorders, will be funded with $6.25 million, part of $51 million put forth by NIH to establish the Rare Diseases Clinical Research Network. The centers will focus on disorders that are often pushed aside in the fight for attention and dollars by more common diseases that affect millions of people, such as cancer, diabetes and heart disease.
The Rochester center will be led by Robert Griggs, M.D., professor and chair of the Department of Neurology. It was Griggs who, 10 years ago, coined the word "channelopathies" to describe diseases caused by abnormal cell channels or gates that regulate the levels of crucial chemicals such as sodium, calcium, and potassium in our cells.
Griggs' center will focus on three channelopathies: periodic paralysis, episodic ataxia, and nondystrophic myotonias. Patients affected by these disorders know all too well the dramatic consequences of the slightest shift in the level of a chemical like potassium in the muscles because of channel problems.
In all three disorders, symptoms are sporadic, triggered in unpredictable ways by factors such as sleep, rest, exercise, diet, being startled, or feeling warm or cold. A patient with periodic paralysis, for instance, might be absolutely fine for years, and then suddenly wake up unable to move a muscle for hours. Other patients might become paralyzed for a few minutes several times every day.
It's much the same with episodic ataxia, except instead of paralysis, patients lose their coordination suddenly and unexpectedly. A person with the cellular defect that causes episodic ataxia might become excited during a sporting event, for instance, and suddenly stagger about with little muscle control and start slurring his or her speech, a condition that can last for seconds, minutes or hours.
In patients with nondystrophic myotonia, a similar cellular defect causes intermittent muscle stiffness. For some patients, exercise eases the symptoms, while for others, exercise makes them worse. Others have no problems working out – it's the resting phase afterwards that worsens their symptoms.
The three disorders are so rare, with perhaps a total of 10,000 patients in the United States, that most doctors never see a single case in a lifetime of practice. Many patients go from doctor to doctor for years before receiving a correct diagnosis from a specialist such as Griggs, who is sought out by patients around the globe who have rare neuromuscular disorders.
Griggs and colleague Rabi Tawil, M.D., associate professor of neurology, treat approximately 100 patients from around the world with these conditions, probably the biggest single pool of such patients anywhere. The two also do basic research on the disease and were part of the team that discovered the genetic cause of periodic paralysis about a decade ago.
The research should benefit more than patients with these three disorders. Griggs notes that within neurology alone, more than 50 diseases are known to arise from problems with channels, including some forms of epilepsy and some migraines.
"This is a good place to start to cure some of these channelopathies," says Griggs. "We're not out just to find a cure for these rare diseases, but to use the information we find to hopefully cure other neurological disorders as well."
With the new funding, Griggs and colleagues will do several studies to move forward effective treatments for these conditions. The team will evaluate several proposed treatments in its studies of episodic ataxia. The myotonia study will focus on mexiletine, a drug now often used to treat heart arrhythmias.
The periodic paralysis study will evaluate the effectiveness of two drugs that have been used occasionally to treat the disorder, to see if the medicine can not only prevent attacks but also help patients improve their strength. The study will focus on Andersen's syndrome, one form of periodic paralysis.
It was as a young researcher at the NIH in the 1960s that Griggs first became interested in periodic paralysis; since then he has played an active role as knowledge has bloomed into a precise understanding of the molecular happenings that bring about the disease.
"This is a disease where patients are completely normal one minute, and then they're paralyzed in all four limbs, for hours or even a day or more, the next," Griggs says. "Now we know exactly what causes the disease, and we're at a point now where we're finally able to establish the best treatment.
"The whole point of the rare diseases program is to support the development of new treatments. These are all diseases where effective treatment is within reach. This program certainly should provide hope for patients," says Griggs.
According to the NIH, approximately 25 million people in the United States are affected by an estimated 6,000 rare diseases or conditions. For them, research usually crawls along slowly, as scientists seek scarce funds to key in on a disease affecting only a few thousand people. Most pharmaceutical companies won't undertake a massive research program where success for patients translates to financial loss because of a tiny market for a new drug. In addition, researchers must find collaborators around the globe to create a pool of patients large enough to do a valid study.
Griggs has pulled together a nationwide CINCH team – Clinical Investigation of Neurologic Channelopathies – to study such disorders. In addition to the University of Rochester Medical Center, other sites include Brigham and Women's Hospital in Boston; the National Institute of Neurological Disease and Stroke in Bethesda, Md.; University of California, Los Angeles; University of California, San Francisco; University of Kansas Medical Center in Kansas City; and the University of Texas Southwestern at Dallas.
Officials say the grant is intended to attract young researchers, just as Griggs' attention was captured by periodic paralysis when he was a new physician.
"A grant like this helps us attract young people who will become interested in these disorders and then will help treat or cure them for decades," says Griggs, whose career investigating rare neuromuscular disorders was inspired when he did some basic research on insect muscle when he was 17 years old. "It takes a great deal of work to understand a disease enough to search for treatments. By focusing attention on these disorders, it will help us attract additional people who will become interested, accelerating the research."
The team will also work closely with patient support groups to reach out to patients and their families. Partners include the Muscular Dystrophy Assn., the Periodic Paralysis Assn., and the National Ataxia Foundation.
At Rochester, in addition to Griggs and Tawil, researchers on the project include Barbara Herr, M.S.; Richard Moxley III, M.D.; and Charles Thornton, M.D.
The University of Rochester is known around the world for its programs training physicians to test new treatments. Currently Rochester is the home base for several large multi-site studies investigating new treatments for Huntington's disease, Parkinson's disease, Alzheimer's disease, and Tourette's syndrome. Under Griggs' leadership, the Department of Neurology now ranks third in the nation in NIH funding among medical school neurology departments. Less than a month ago, the department was also named by NIH as one of three newly created muscular dystrophy cooperative research centers.
The other six rare-disease centers established this week by NIH will focus on a variety of topics, including rare lung diseases, bone marrow failure, and genetic steroid disorders.
"Funding research on rare diseases is a vital aspect of the NIH mission," says NIH Director Elias A. Zerhouni, M.D. "By encouraging cooperative partnerships among the investigators at these centers, we hope to accelerate the development of diagnostics and treatments that will benefit these important patients."