Geneticist Haydeh Payami, PhD., has made it her life’s mission to prevent parkinson’s disease (PD) in individuals who are genetically prone to the debilitating condition, and to devise effective personalized treatments for people who already have the disease. To achieve these lofty goals, Dr. Payami, who earned a PhD in genetics from University of California, Berkeley, was the first researcher to decipher the genetic component involved in PD, is the founder and leader of the NeuroGenetics Research Consortium, which has amassed 4,000 highly diverse genetic samples making it the most distinctive PD data set of its kind; and is currently a professor of neurology at University of Alabama (UAB), as well as a faculty investigator at the HudsonAlpha Institute for Biotechnology.
Dr. Payami’s lab at UAB and the HudsonAlpha Institute is utilizing the latest genetic sequencing and analysis technology to discover the genes that interact with environmental risk factors to predict who is at risk and what they should avoid, and the genes that determine success and toxicity of drugs for prevention and treatment, so that prescribed therapies can be personalized for maximum benefit of each patient. The lab is also interested in gaining an understanding of how the disease develops, why it progresses, why it affects so many systems of the body (physical and cognitive, psychiatric, digestive), and how best to stop it.
Dr. Payami and her research team are currently studying individual genetic variation as it relates to the protective power of coffee, nicotine and NSAIDs (anti-inflammatories such as ibuprofen) as well as looking at the possible damage caused by the immune system and microbiome in patients with PD. In a series of experiments and genetic analyses that Dr. Payami calls “fishing expeditions,” in which the objective is to find genetic clues to answer questions such as:
- Why do smokers and coffee drinkers have a much lower risk of getting the disease?
- What role does the immune system play in PD?
- Why do some people get the disease in their teens, while it appears in others in their late 80s?
In a recent University article, Dr. Payami discusses the impact of her work and its future direction.
The Power of Caffeine
In a study entitled, “Genome-Wide Gene-Environment Study Identifies Glutamate Receptor Gene GRIN2A as a Parkinson’s Disease Modifier Gene via Interaction with Coffee,” published in PLOS Genetics, Dr. Payami, and her team analyzed DNA sequences from the genome of 1,458 patients with PD and 931 healthy controls, and looked for genetic variations in heavy coffee drinkers (around 2.5 cups per day and higher for 25 years) in relation to their PD risk.
They found 2 important genetic variants that had a protective effect in heavy coffee drinkers:
- a gene called GRIN2A
- a gene called MAPK10
In a statement about the study’s findings, Dr. Payami, said “GRIN2A produces a receptor for glutamate, an important signaling chemical in the brain. Balancing glutamate on neurons is critical for neuronal toxicity. And glutamate toxicity is one of the suspected mechanisms in the cell death we see in Parkinson’s. So you can imagine that if you have a problem with the receptor, your risk will be higher.”
Dr. Payami continued, “If you just ask people how much caffeine they drink and map that, you see that the risk for Parkinson’s drops by about 30 percent in heavy caffeine drinkers. And then there’s this lucky 7 percent, who have about an 87 percent risk reduction. So there are people who should be drinking lots of coffee — or consuming a prescribed, regular dose of caffeine in pill form, perhaps. Many people will see no benefit; but for some people, it will drastically reduce their risk of getting Parkinson’s. We have to figure out the right dose, because too much caffeine can be harmful, even fatal.”
The Power of Nicotine and NSAIDS
In a study entitled, “A genetic basis for the variable effect of smoking/nicotine on Parkinson’s disease,” published in Nature’s The Pharmacogenomics Journal, Dr. Payami, and her team discovered the same pattern they observed in smokers. As Dr. Payami, explains it, “If you divide people between those who smoked regularly and those who never smoked, there’s clearly a 25 percent lower risk of Parkinson’s disease among the smokers.”
The difference was based on variations in a specific gene called, SV2C. The researchers also observed a genetic susceptibility difference among individuals who frequently took NSAIDs.
Currently, there are 2 major clinical trials taking place that are studying the effects of caffeine and nicotine on PD. As Dr. Payami, explains, “These trials had already started when we discovered the genes, and the PI came up to me to suggest a collaboration after a talk that I gave. The investigators leading both trials are now drawing blood on their patients, and we’re going to genotype them here.”
If you want to help
Dr. Payami will be starting a trial in the near future. As she explains it, “We’d like to genotype tens of thousands of people who do not have the disease. We want to follow them and see who is going to get the disease when, and who is not — and whether that is related to how much they smoked or did not smoke and how much caffeine they took or what kinds of diseases they had, whether they are using inflammatory drugs or not, and so on. If companies bought into this, we could advertise it nationally and recruit tens of thousands of people to join,” she said. “They would each send in a saliva sample, and we could sequence their whole genome from that. Then they could go online every six months and update us on how they’re doing — as well as lifestyle factors, what they’re taking as far as inflammatory drugs, how much caffeine they are drinking, whether they are smoking.”
Dr. Payami, adds “With a large enough sample, you could have all the answers in five years, plus another few years to do the math and develop the algorithm that will say who would most benefit from caffeine, nicotine and anti-inflammatory drugs.
For more information on Dr. Payami’s research and opportunities to take part in this trial please click here.
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