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Aspirin for Parkinson's: What Does It Mean?

Can an aspirin a day treat Parkinson’s disease (PD)? Not exactly, but the idea made headlines a few weeks ago, after scientists discovered that a key ingredient of aspirin might have potential to block the loss of brain cells in neurological diseases like PD and Alzheimer’s.

As with every science headline, the Parkinson's Foundation asks, "what does it mean for people with PD?" In this case, we asked Michael Schwarzschild, M.D., Ph.D., of MassGeneral Institute of Neurodegenerative Disease, a well-known PD scientist who has also studied aspirin and ibuprofen in relation to PD. Here are his insights.

Q. Several years ago, you and your colleagues also studied whether non-steroidal anti-inflammatory drugs (NSAIDs) like aspirin and ibuprofen might impact PD. What did you conclude from your investigation?
A. Yes, our team conducted an epidemiological study to find out whether people who take NSAIDs might be at a different risk of developing PD later on, compared to people who don’t take them. There is evidence from our study and others that NSAIDs are linked to a slightly reduced chance of getting PD. However, a closer look at the data, has revealed that ibuprofen and other NSAIDs but not aspirin are linked to reduced PD risk.

Q: Last week, a different study published in PLoS ONE (available here) found that aspirin might have potential for helping to stop PD. Can you tell us about the results? 
A. When we take aspirin, the body converts it into a compound called salicylate. In the new study, researchers found that salicylate was able to block the activity of an enzyme that has been indirectly linked to PD, called Glyceraldehyde 3-Phosphate Dehydrogenase, or GAPDH. Right now, it may be difficult to translate these results into new treatments or practical recommendations for use of aspirin. More research is needed. But the results might lead to further research into GAPDH and how it works in PD.

Q. Should people with PD (or those worried about developing PD) start taking aspirin?
A. Taking aspirin can be helpful for reasons other than PD in some individuals. But taking aspirin to slow or prevent PD is not good clinical advice given both the conflicting and incomplete evidence to support its benefit against PD, and given that aspirin (like any drug) can have side effects.

Q. The authors of the study point to selegiline (Deprenyl®), a commonly prescribed drug in PD, as potentially having the same neuroprotective effects as aspirin. Can you explain?
A. Deprenyl provides mild relief of movement symptoms for people with PD. We think it helps in PD because it boosts brain levels of dopamine (the neurotransmitter that is low in PD). It is true that laboratory studies have shown that deprenyl can protect brain cells in animals, but this has not yet been proven in humans.

Q. Have researchers tried to see if deprenyl (Selegiline®) can stop PD in people?
A. Yes, there was a study called the DATATOP trial, which was the first large-scale clinical trial to test potential treatments for their ability to slow progression of PD. In that trial, deprenyl was found to be helpful for people with early PD. But researchers think this improvement was due to the drug’s impact on symptoms, not any impact on the long-term progression of the disease.

Q. How does the aspirin study advance our goal of developing new therapies for PD?
Paradoxically, the study is both too early and too late in terms of drug development. Early because although the study has shown us that salicylate can affect the enzyme GAPDH, we still don’t know if this is related to PD. Thus, we need more research in PD-specific models. Late, because the authors offer two drug compounds that could target the body in the same way as aspirin. These are deprenyl and the experimental compound TCH346. Both compounds have already been studied in clinical trials in the hope that they might slow PD progression, and showed no convincing evidence of doing so. Those results do not disprove their protective potential, but they lessen enthusiasm for more clinical trials of similar drugs.

Q. If the research hasn’t yet proven that aspirin or selegiline can slow PD, are the results helpful for Parkinson’s science?
Yes. In fact, the finding that salicylate from aspirin can target GAPDH is even more interesting now that preliminary evidence (see here and here) shows that a gene variation related to GAPDH has been linked to PD. Together the findings, if confirmed, should lead to more research (lab and epidemiological) about possible links between aspirin use or GAPDH gene variants and PD progression or risk.

 Dr. Schwarzschild is a Parkinson's Foundation-funded researcher who has conducted similar research (initially launched with foundation funding) into urate and Parkinson's. In 2016, he and his team will open a Phase III clinical trial, testing the potential of the nutritional supplement inosine (which converts to urate in the body) as a treatment for PD.

 

Category: 
Research Round Up
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