Researchers have found a gene that may explain why coffee may lower the risk of Parkinson's disease for some people, and that might explain why some experimental drugs do not appear to be working.
About a quarter of the population carries this version of the gene, and drug developers may be more successful if they test people for it, Haydeh Payami of the New York State Department of Health told the World Parkinson Congress in Glasgow on Wednesday.
Only people with this particular version of the gene are likely to be helped by an experimental class of drugs designed to mimic some of coffee's benefits, Payami told the meeting.
We are trying to explain why some people benefit from the effects of coffee in terms of reducing the risk of getting Parkinson's disease and others don't, Payami said in a telephone interview.
But by extension I am proposing that this translates into explaining why drugs that are like caffeine that are in clinical trials are not succeeding, she added.
The immediate application right now would be for people who already have Parkinson's.
Currently, Parkinson's patients with and without the specific gene are being included in the trials.
Her team studied 4,000 people, half with Parkinson's, using an Illumina gene chip to look at the entire genetic map of each volunteer, a technique called a genome wide association study.
They identified a gene called GRIN2A that appeared to protect people who drank coffee from developing Parkinson's.
About 25 percent of the population has the variant that boosts the protective effect of coffee, Payami said.
This made sense to Payami, whose team's work is funded by the National Institute of Neurological Disorders and Stroke, the nonprofit Michael J. Fox foundation and other groups.
GRIN2A is linked to glutamate, a compound that is suspected of killing the brain cells that die off in Parkinson's patients. Glutamate can be affected by another compound called adenosine, and coffee interferes with this process.
Drugs called adenosine A2A receptor antagonists have been tested against Parkinson's and other neurological diseases. Payami said her team's genetic findings may help explain the disappointing results of those trials so far.
If this gene really is interacting with coffee to boost neuroprotection, it should work in these clinical trials, she said.
Caffeine has been shown to protect nerves, but it has some unappealing side-effects, including jitters. Payami said the drugs are designed to reduce these side-effects.
I think it is about time we brought genetics into the design of clinical trials for Parkinson's disease, she added.
This work shows the potential of using genetic and epidemiological approaches to identify new risk factors for Parkinson's disease, said Margaret Sutherland of the NINDS, one of the U.S. National Institutes of Health.
Parkinson's is a fatal and incurable brain disease that affects 1 percent to 2 percent of people over 65. It can begin with tremors, sluggish movement, muscle stiffness, and difficulty with balance.
Drugs such as levodopa, GlaxoSmithKline's Requip, or ropinirole, and Boehringer Ingelheim's Mirapex, or pramipexole, can improve symptoms for a while.