One Major Step Forward for Parkinson's Sufferers
All smiles and for good reason: Researchers Roger Duvoisin,
Alice Lazzarini, Lawrence Golbe, Edward Stenroos and Willian Johnson
Many years of work by faculty members of the Department of Neurology at UMDNJ-Robert Wood Johnson Medical School recently culminated in a breakthrough in Parkinson's disease research. They identified a small region on chromosome 4 as the site of the gene mutation that caused the disease in 60 members of a large multi- generational family. The finding was reported in the November 15th issue of the journal Science.
Roger Duvoisin, MD, recently retired chair of the department and now Lovett professor emeritus, spent most of his career wrestling with the roles of heredity and environment in Parkinson's disease. Earlier epidemiological surveys and studies of twins proved inconclusive, but in 1980 he began studying patterns of inheritance in familial clusters of the disease. Working with Lawrence Golbe, MD, Margery Mark, MD, and later William Johnson, MD, he collected a number of multi-case families. Johnson, director of the Lovett Laboratory of Neurogenetics, stored DNA collected from these families and initiated a search for a DNA marker linked to the disease.
One family of Italian origin identified 10 years ago by Golbe in the medical school's neurology clinic was eventually found to comprise over 400 individuals. So far, at least 60 cases of Parkinson's disease have been identified in the last five generations in this family.
With the aid of colleagues at the University of Naples, Italy, Golbe was able to establish the full genealogy of this family through 12 generations to an ancestral couple who lived in the village of Contursi in southern Italy in the early 18th century. His examination confirmed that the family disease was in fact Parkinson's, and showed for the first time that Parkinson's disease could occur on a genetic basis.
Meanwhile, Alice Lazzarini, PhD, assistant professor of clinical neurology, carried out a
study of familial aggregation in Duvoisin's personal patients and established that a large subset of Parkinson's disease cases are familial. Her analysis of 80 multi-case families drawn from the medical school's neurology clinic defined the pattern of inheritance as autosomal dominant.
In October 1995, Duvoisin, Johnson, Golbe and Lazzarini began a collaborative effort with Robert Nussbaum, MD, and Mihael Polymeropoulos, MD, at the National Center for Human Genome Research and Joseph Higgins, MD, at the National Institutes of Neurological Disorders and Stroke, to locate the gene mutation in the Contursi kindred. In less than a year, they had linked the disease to DNA markers for a small region of chromosome 4.
The discovery not only confirmed that Parkinson's disease can occur on a genetic basis, but also showed that a mutation in a single gene is sufficient to cause the disease. "The next step is to isolate the specific gene and identify the mutation," says Duvoisin. "Then we can learn how the mutation causes the disease and ultimately develop methods of prevention and even of cure."
The research group anticipates that clarifying the molecular genetic mechanism of the disease in the large extended Contursi family will yield invaluable insights into the biological mechanisms underlying all cases of Parkinson's disease, whether sporadic or due to mutations in another gene.