Rochester Neurologist to Head Largest Study Ever of Rare Paralysis
February 27, 2004
"It may be hard to believe, but some patients don’t recognize it when they’re paralyzed."
A University of Rochester neurologist will lead the largest study ever of a rare inherited disease that leaves patients unpredictably paralyzed for minutes or hours at a time.
Robert Griggs, M.D., professor and chair of the Department of Neurology, has received $5.7 million from the National Institute of Neurological Disorders and Stroke to study patients with periodic paralysis. Doctors plan to include 252 patients in the five-year study to take a close look at two possible treatments for the disease. Since periodic paralysis is so rare, with only a few hundred patients in the United States, Griggs has established a network of 14 centers across the United States, Canada, and Europe to work together.
Symptoms of the disease are sporadic and are affected by factors such as diet, rest and exercise. Some patients have no symptoms for years; others struggle with paralysis every day.
“In severe cases, a patient can wake up with weakness every morning, for several hours,” Griggs says. “It may be hard to believe, but some patients don’t recognize it when they’re paralyzed. Patients may wake up and simply not be able to move for three or four hours, and they say they just have a difficult time getting going in the morning, like a lot of people do. But these patients are indeed abnormally weak – and that may contribute to permanent paralysis eventually.”
Scientists will evaluate the effectiveness of the two drugs most commonly used to treat the disease, to see which is more effective and to study the long-term effects of both.
It was more than 35 years ago that Griggs first showed that one of the drugs, acetazolamide, is somewhat effective for treating the disease. But the medication carries some side effects, such as a higher likelihood of getting kidney stones, and so many patients and their doctors choose not to use it. In addition, doctors don’t know whether the drug stems the progressive weakness and the loss of muscle often seen in patients as they undergo repeated episodes of paralysis.
The other drug that doctors will test is dichlorphenamide, which Griggs and colleague Rabi Tawil, M.D., showed four years ago to be useful in treating the disease and at keeping patients’ muscles strong. But the medication is used only rarely and has been taken off the market because it was too costly to produce.
Griggs hopes to show which of the two treatments better prevents attacks. He also thinks that treatment may even reverse the muscle weakness that now is inevitable. He’s also hoping to pinpoint just how people will respond to treatment based on the genetics of their particular cases.
While it’s an extremely rare disorder, the study should help scientists understand dozens of diseases, Griggs says. Periodic paralysis is one type of “channelopathy,” diseases caused by abnormal cell channels or gates that regulate the levels of crucial ions such as sodium, calcium, potassium and chloride in our cells. When the amount of these ions in our muscles and other tissues is off by just a tiny bit, disease is the outcome.
Periodic paralysis is one of three uncommon neurological disorders that Rochester scientists are studying as part of a new network of research centers established by the National Institutes of Health recently to investigate especially rare diseases. The current study is known as the “HypHop” study, referring to forms of periodic paralysis that are either hyperkalemic (hyp) or hypokalemic (hop).
In addition to Griggs and Rabi Tawil, M.D, who were part of the team that discovered the genetic cause of periodic paralysis a decade ago, the current study at Rochester involves neurologist Emma Ciafaloni, M.D.; biostatistician Michael McDermott, Ph.D.; and more than a dozen others, including nurses, statisticians, programmers, and other support personnel.
Other U.S. sites for the study are Harvard Medical School, Boston; University of Kansas, Kansas City; Mayo Clinic, Rochester, Minn.; National Institutes of Health, Bethesda, Md.; University of Texas at San Antonio, Texas; University of Texas Southwestern at Dallas; Ohio State University in Columbus, Ohio; Columbia-Presbyterian in New York City; and University of California at San Francisco.
International sites are the London Health Science Center, in London, Ontario, Canada; the National Hospital at Queens Square, London, United Kingdom; San Donato Medical Institute, Milan, Italy; University Hospital, Groningen, Netherlands; and Petie-Salpetriere, Paris, France.