Trials of Autophagy Enhancement to Treat Parkinson’s Disease


Researchers are planning trials of a repurposed drug in order to test the effectiveness of enhanced autophagy to treat Parkinson’s disease, a condition characterized by loss of the small population of dopaminergenic neurons in the brain. Autophagy is a cellular housekeeping method, and the various genes associated with Parkinson’s suggest that the underlying disease mechanism is made worse by inadequate clearance of damaged mitochondria in neurons. Beyond Parkinson’s disease, methods of producing increased autophagy are of general interest to those who would like to slow the aging process. Greater levels of autophagy are observed in many of the interventions demonstrated to modestly slow aging in laboratory species, but despite that there has been so far little progress in moving towards clinical therapies based on enhanced autophagy. We should probably expect only marginal results from this particular trial, but it will hopefully help to pave the way for future efforts that do more to boost autophagy in a targeted, deliberate way.

Scientists are hoping that a single drug can treat two devastating brain diseases: Parkinson’s and Alzheimer’s. The drug is nilotinib, which is approved to treat a form of leukemia. In late 2015, researchers found that small doses of the drug appeared to help a handful of people with Parkinson’s disease and a related form of dementia. They’d tried the unlikely treatment because they knew nilotinib triggered cells to get rid of faulty components – including the ones associated with several brain diseases. Results of that preliminary study generated a lot of excitement, but many researchers were cautious. “It was such a small trial, there was no placebo control and it really wasn’t designed to assess efficacy.” So the original researchers are launching two larger and more rigorous trials of nilotinib, both designed with input from the Food and Drug Administration. One of the trials will enroll 75 patients with Parkinson’s disease, the other will enroll 42 patients with Alzheimer’s.

Nilotinib seems to work by eliminating toxic proteins that build up in the brains of people with Parkinson’s and Alzheimer’s. The drug activates a mechanism in brain cells that acts like a sort of garbage disposal. “Our drug goes into the cells to turn on that garbage disposal mechanism. And if we’re able to degrade these proteins, we could potentially stop the progression of this disorder.” The primary goal of the studies is to learn whether this powerful cancer drug is safe enough for patients with brain diseases. But the new studies should also provide better evidence about whether the drug really works. There’s good reason for patients with Parkinson’s, Alzheimer’s and other neurodegenerative diseases to be optimistic these days. Drugs like nilotinib are coming along because years of research have provided a much better understanding of how these conditions damage the brain. “Now we’re in the payoff phase.”


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