This three-year grant strengthens the research arm of the Medical Center's ALS clinic, one of the largest treatment centers for the disease in Pennsylvania. ALS is a neurodegenerative disease that starts with muscle weakness and progresses to loss of muscle function and death. There is no known cause of the disease and no known treatment.
PGA golfer Tom Watson and his caddie, Bruce Edwards, recently have brought a great deal of attention to the disease since Edwards' diagnosis in January 2003. About 30,000 people in the U.S. live with ALS and sufferers usually survive five years or less after diagnosis. "Because so little it known about ALS, a number of our families from the clinic have been working with us to raise funds to support ALS research," said Zachary Simmons, M.D., professor and interim chair, Department of Neurology, and director of the ALS Clinic at Penn State Hershey Medical Center. "This award makes it possible for us to look into possible causes and risk factors of ALS and add to what little information is known about this disease."
In a preliminary study of 74 people diagnosed with ALS, Simmons and research partner James R. Connor, Ph.D., professor of neural and behavioral sciences, Penn State College of Medicine, found that there is a high prevalence of a mutation in a gene called Hfe in ALS patients.
"This suggests that the Hfe mutation is a risk factor for ALS," Connor said. "This grant will allow us to expand the number of individuals we can test with and without diagnosed ALS and continue our studies to see how the mutation affects onset and progression of this disease."
For the study, Connor and Simmons will identify patients with ALS and those with other neuromuscular diseases and look for the prevalence of the mutated form of the Hfe gene in the two groups. A mutation in the Hfe gene has been linked with a condition called hemachromatosis, which causes too much iron to accumulate in the tissues. People can be carriers of the mutant Hfe gene and yet have no symptoms of hemachromatosis. However, the organs (e.g. liver, heart, brain) of these individuals may still mishandle iron and as a result can produce free radicals. Free radicals are toxic forms of oxygen that result when iron interacts with oxygen in the body. These toxins can indiscriminately kill healthy cells. This process, called oxidative stress, is considered a contributor to the disease process in ALS.
Connor and Simmons will test the hypothesis that Hfe mutations are associated with an earlier onset of ALS and a more rapid disease progression. A second part of the study will investigate distribution and levels of expression of Hfe in tissue collected at autopsy from the brains and spinal cords of those with and without ALS. Finally, because the researchers hypothesize that the presence of an Hfe mutation increases the amount of oxidative damage, they will measure the amount of oxidative stress markers in autopsy samples from those with ALS and the Hfe mutation, and compare it to samples from patients with ALS without the mutation. An important component of ALS research is organ and tissue donation when a person with ALS dies.
"We deeply appreciate such donations, and fully realize what valuable gifts these are," Simmons said. "We believe there are exciting therapeutic opportunities that may result from our study. If our hypothesis proves correct, those patients with ALS who possess the Hfe mutation could be counseled to reduce dietary iron intake and may respond particularly well to antioxidant therapy."
For more information about donating tissue after death, call Simmons' office at 717-531-1802. To make an appointment with the ALS clinic, please call 717-531-1441.