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Come Together Over Parkinson's


In 1992, Haydeh Payami was a professor at Oregon Health and Science University when one of her undergraduate students asked to begin a project examining the genetics of Parkinson's disease. At the time, research on the neuro-degenerative disease was focused primarily on the environmental effects that appear to play a role in its development and progression. In the early 1990s, little attention had been paid to the possibility that genetic polymorphisms could affect an individual's susceptibility to the disease.

The student "would not take 'no' for an answer," Payami says. "She lit the fire underneath me." Payami approached John Nutt, the director of the OSHU Parkinson Center of Oregon, to initiate a genetics study. Payami says that Nutt told her: "Sure, here's my clinic. Go."

Since then, Payami and others have identified and replicated several Parkinson's susceptibility genes. Her National Institute of Neurological Disorders and Stroke grant to analyze the genetics of the age of onset of Parkinson's has just been approved through 2013.

Payami was still working with Oregon's Nutt and their collaborators at the University of Washington in Seattle when she moved to the New York State Department of Health Wadsworth Center in 2003. While at Wadsworth, Payami began to work with Stewart Factor, who was a professor of neurology at the Parkinson's Disease and Movement Disorders Center at Albany Medical Center. From October to December 2003, Factor worked with Payami and together they submitted an application for funding through the Michael J. Fox Foundation's Edmond J. Safra Global Genetics Consortia initiative.

With a two-year award in hand, Payami, Factor, Nutt, and Washington's Cyrus Zabetian established the Neurogenetics Research Consortium, which, according to Payami, "is the most informal group that I know of. It's a small group of investigators who are totally, totally dedicated to what they're doing," she says. So dedicated, in fact, that they have remained active several years beyond the expiration of their MJFF award, which was their only source of group-specific funding.

"We don't have funding for our consortium, per se. One of the requirements for being part of our consortium is that you're willing to do the work no matter what and trust that we'll all work hard to get the funding to get it done," Payami says.

It has been the NGRC's continued success, fueled by a unique blend of give-and-take — as demonstrated by the flexibility it has allowed its members in terms of financial contributions — that makes this collaboration so uncommon. According to Payami, "we don't stop and say, 'OK, we don't have money so we can't go forward.'" Instead, she says, the team maintains the attitude that "we can generate so much [interesting data] that we can get the funding to move forward. ... We just want to beat Parkinson's disease whatever it takes," she says. In tough times, NGRC has looked to its members to fill funding gaps. Currently, the group is supported by two NINDS grants as well as funding from the Department of Veterans Affairs and nonprofit organizations such as the Charlotte, NC-based Close to a Cure, among other agencies.
Teamwork pays off

Time and again, Payami says, their teamwork has paid off. Most recently, NGRC published results of a genome-wide association study of 2,000 Parkinson's patients and 1,986 controls in Nature Genetics in August. They detected a novel association in the HLA genomic region with late-onset, sporadic Parkinson's disease.

"Our study confirmed the associations with a-synuclein and Tau — those are the two most strongly associated genes — but we also found an association with this HLA-DRA gene, which is on chromosome 6 and is highly significant," says Factor, who now directs the Movement Disorders Program at Emory University. The team also tested these associations against a set of environmental factors — including caffeine intake, head trauma, non-steroidal anti-inflammatory drug use, and smoking — and confirmed that smoking, caffeine, and NSAID use show an inverse relationship with Parkinson's disease risk. Factor says that the team enrolled the nearly 4,000 participants across the four centers. "You really need several thousand samples in order to do this type of study. … It took us five to six years to collect all the samples," he says, adding that NGRC reached out to epidemiologists when collecting environmental exposure data.

"Everyone sort of put in their own: the clinicians collected clinical data, the geneticists [said], 'We need to collect the DNA and standardize the process of sequencing genes,' and the epidemiologists were able to help us with doing the questionnaires for exposures appropriately," Factor says.

After discovering the HLA-DRA hit, Payami reached out to Henry Erlich at Roche to propose a deep-sequencing project. "HLA deep sequencing is really, really difficult ... so we went to the world expert," Payami says. "That's how we operate. You go with a project, you get people interested, they jump in, you put in a [supplemental grant application] … and you run with it."

NGRC hopes to see the results of the sequencing project within the next six months. From there, the group's research possibilities — as well as their motivations — are endless, Payami says.

A successful collaboration is achieved in the end, she says, by pairing those with similar motivations together to achieve a common goal. It is imperative "that style does not come in the way and delay progress," Payami says. "You just have to find like-minded people and work with them."

The Breakdown

Members: New York State Department of Health, Oregon Health and Science University, University of Washington, Emory University
Funding: Sources vary. Currently funded by grants from NINDS as well as the Department of Veterans Affairs and nonprofit organizations.
Timeframe: Established in late 2003; active, ongoing collaboration.

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