Searching for a biomarker for Parkinson’s disease

It was a pretty spring day in April of 2007, and George Andrews had his arm out the car window as he drove into work. He noticed his thumb twitching, and that brought back memories. His mother had been diagnosed with Parkinson's disease in the 1980s, and a twitching thumb was the very first symptom anyone in the family noticed.

Andrews knew how bad Parkinson's could be. He'd watched his mother through the last six years of her life, living in a nursing home, unable even to eat on her own. And now his thumb was twitching on his car door.

A trip to a neurologist confirmed that Andrews also had Parkinson's. Since then, he's been able to control his symptoms with medications, many of which didn't exist when his mother was diagnosed. But even the newest Parkinson's therapies can only mask symptoms while the disease continues to worsen over time.

The goal is to develop treatments that could slow or stop the progression of Parkinson's, maybe even before a thumb starts to twitch. That effort has proved exceptionally difficult, though, without a critically needed research tool called a biomarker.

Biomarkers are objectively measurable physical characteristics associated with the risk, presence or progression of a disease. The prostate-specific antigen, or PSA, test for prostate cancer is one good example of a useful biomarker. In the past month, researchers also reported the discovery of an Alzheimer's disease biomarker in a spinal fluid test.

Reliable and consistent biomarkers enable scientists to predict, objectively diagnose and monitor diseases, as well as help determine which medications work and which do not. There is currently no known biomarker for Parkinson's. But now, UAB is part of the most comprehensive search for Parkinson's biomarkers to date, as one of 18 official study sites for the Parkinson's Progression Markers Initiative (PPMI).

PPMI is a landmark, five-year, international clinical study to identify biomarkers of Parkinson's disease progression. This study will use a combination of imaging techniques, the collection of blood, urine, and spinal fluid, and clinical tests to identify a biomarker that can be used for the development of new and more effective treatments for Parkinson's disease. PPMI is sponsored by The Michael J. Fox Foundation.

"This is a lever that might help open the door to a potential cure for Parkinson's," says David G. Standaert, M.D., Ph.D., professor in the Department of Neurology and UAB's principal investigator for PPMI. "UAB has built a world-class team in Parkinson's disease research in Alabama. PPMI is a novel and challenging project, and there is no guarantee that validated biomarkers will be found. But we believe the importance of these tools to therapeutic progress requires that we accept this risk."

With Parkinson's disease progression biomarkers in hand, researchers can start testing ways to modify Parkinson's treatments  - concrete ways to demonstrate that a candidate therapy is, or is not, having an impact on the course of the disease in patients, as opposed to simply affecting symptoms. Without a biomarker, this sort of evidence-based decision-making is not possible.

"For example, we may develop a new agent with great promise to slow the progression of Parkinson's," says Standaert. "Without biomarkers, we might have to follow a patient for years waiting to see if the drug actually proves to be effective. With suitable biomarkers, we might know in six to 12 months if a therapy is working and worth pursuing further."

Andrews is excited about the biomarker research and what it may mean for patients.

"I'm like a cheerleader on the 50-yard line, urging the researchers forward," he says. "This is what I love about UAB, the work under way there to better understand diseases like Parkinson's, and to find ways to treat, slow or even cure them entirely."

Michael J. Fox acknowledges that PPMI is an ambitious undertaking. "But nothing worth having comes easily," Fox says. "Everything we've learned up to now, the partnerships we've worked to forge, the results of research we've funded - it's all put us in position to launch this effort.

"We're ready to roll up our sleeves and, hopefully, get this done."

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