While Robert Smith, a professor of medicine at the Alpert Medical School, was researching diabetes, he discovered something key to understanding another illness - a gene that could be the link to Parkinson's disease in patients with a family history of the disorder.
Smith, the director of the Division of Endocrinology at Rhode Island Hospital, led the study with researchers at the Med School, Rhode Island Hospital and in Milan and Paris. Five years ago, Smith and his colleagues took notice of the gene, GIGYF2, while researching diabetes - his usual field of study - because it seemed that it may be involved in the production of insulin, according to a University press release.
When the researchers tried to understand the functions of the protein for which the gene codes, Smith said their normal methods proved unsuccessful. The researchers then looked to the Human Genome Database to understand the function of the protein.
"We asked the question: Are there any other diseases that are encoded in this region?" Smith said. According to the press release, once they found out that GIGYF2 was right in the middle of a chromosomal region associated with Parkinson's disease, "it was enough to get us diabetes people to work," and the scientists "decided to take a risk and determine if there was a link," he said.
In the United States, about 60,000 new cases of Parkinson's disease are diagnosed annually, in addition to the 1.5 million Americans who currently have the debilitating movement disorder, according to the National Parkinson Foundation Web site. Currently, medicines and surgery can treat the symptoms of the disease, but there is no cure, according to the Web site.
In the study, researchers analyzed DNA from about 250 people with familial Parkinson's, meaning that a parent, sibling or child also had or currently has the disease. An additional 200 healthy DNA samples from the same French and Italian populations were also studied as a control group, according to a University press release.
The findings of the research, published online in the American Journal of Human Genetics on March 20, explain that the scientists found seven different mutations of gene GIGYF2 in 12 unrelated individuals with familial Parkinson's, which accounts for 4.8 percent of the sample.
Smith said the link between the genetic mutations of GIGYF2 and Parkinson's disease is a "highly significant association."
Only about 10 to 30 percent of cases of Parkinson's disease are characterized as familial, and the sporadic forms of the disease are more common, according to information cited in the study. But learning about the familial form of the disease is valuable because the genetic links are "expected to define mechanisms and new therapeutic approaches" that are relevant to other forms of Parkinson's as well, the study says.
"If we find out what the gene does - if we understand the functions of the protein - we can understand the pathways, which will give us insight," Smith said.
To determine the function of the protein coded by this gene, the research team is developing a genetically engineered mouse in which they will partially or completely eliminate GIGYF2 and "question whether it produces something like Parkinson's," Smith said.
By studying the physical effects of the altered gene on the mice, the scientists will gain a better understanding of the causal relationship between the gene and Parkinson's disease, Smith said. The scientists will also study the protein in culture, Smith said, to look for changes in functionality when protein levels are raised and lowered or when mutated versions of the protein are introduced.
Smith said the study's immediate potential to be broadly applied is limited since it included subjects with familial Parkinson's evidenced by only a few family members and the DNA was not available for all family members in question.
"The ultimate breadth of application is going to take time," Smith said. If the researchers find a family with many individuals both affected and unaffected by Parkinson's disease, they would be able to study the gene in question more extensively, he added.
Since people who have Type 2 diabetes are twice as likely to develop Parkinson's, Smith said the possibility of a link between the diseases is interesting. He said he plans to continue studying both diseases.
"What has us most intrigued is that as we learn more about the protein, it may help us learn more about the link between diabetes and Parkinson's or the link between diabetes and other neurodegenerative diseases," he said. "We have the promise of bridging diseases."
