Mayo Magazine

Searching the Genome — Clues to Parkinson's Disease

Today, Parkinson's disease is largely a mystery to physicians. No single test, except an autopsy, can accurately diagnose the disorder, current treatments only relieve symptoms and little is known about factors that influence disease progression.

But genomics research at Mayo Clinic, led by Demetrius M. Maraganore, M.D., may change that picture, and, in as little as five years, give physicians the ability to diagnose and treat the disorder with much greater efficacy. With funding from the Michael J. Fox Foundation, Dr. Maraganore and colleagues from Mayo Clinic Rochester and Mayo Clinic Jacksonville are collaborating with a team from Perlegen Sciences, a biotechnology company dedicated to personalizing medicine through genomics, to complete the first largescale, whole-genome map of genetic variability associated with Parkinson's disease.

Comparing and contrasting DNA

It is one of the first studies of its type for any disease, and it analyzed deoxyribonucleic acid (DNA) from 775 people with Parkinson's disease and compared this information with study results from 775 people without the disease. In doing so, researchers identified 12 genes that may increase the risk of developing the disease.

The findings from this first study will need to be validated in a larger study, says Dr. Maraganore. That work has already begun, with assistance from centers around the world. In addition, it is likely that several genes act in combination to influence a person's risk of Parkinson's disease, Dr. Maraganore says, and tools are being developed that will allow him to extract this information from the study as well.

Nonetheless, even if only one of the genes identified in this initial run is validated through further testing, it still represents an important step forward in treating Parkinson's disease, Dr. Maraganore says.

"Every time a new gene for the disease is discovered, it's potentially a breakthrough because it confirms that a previously recognized mechanism for the disease is important, or it unveils a new mechanism," Dr. Maraganore says. "Understanding these mechanisms is how we identify targets for therapies that can slow or halt the disease."

A wealth of information

The study also will help researchers throughout the field because its huge collection of data will be publicly available, says Matthew J. Farrer, Ph.D., a scientist at Mayo Clinic Jacksonville.

"It's a gold mine," Dr. Farrer says. "No one's ever built a database of this size with genetic information on Parkinson's disease. Scientists throughout the world will want to look at it, to investigate Dr. Maraganore's results and to advance their own research."

That gold mine of information contains data from more than 155 million genetic tests. The Perlegen group has created a technique for whole genome association that quickly collects data on 200,000 points or base pairs of DNA in each research participant. Though the human genome contains some 3 million base pairs, Perlegen says their studies show that they can capture more than 80 percent of the variability in the human genome by measuring it at 200,0000 selected areas.

In addition to yielding information about genetic risk factors for Parkinson's disease, Dr. Maraganore says the next step is to probe the data to gain insights about the connection between genes and therapy response, disease progression and other prognostic indicators. The results could mean that, in a relatively short time, physicians will be able to look at Parkinson's disease from an entirely different perspective.

"Within five years, we could predict with a great deal of accuracy who will get Parkinson's disease and also what therapeutic developments can significantly slow or halt the disease." Dr. Maraganore says.