One of the most promising treatments for Parkinson’s disease has hit a snag after researchers found evidence that it may make patients worse. ELN, Alnylam Pharmaceuticals, NeuroPhage Pharmaceuticals, and Prana Biotechnology are all developing drugs that target a protein that appears in large concentrations in the brains of those afflicted with the progressive neurological disorder. The foundation started by actor Michael J. Fox, who was diagnosed with Parkinson’s in 1991 at age 30, has poured more than $47 million into research on the protein.
While a variety of medicines relieve symptoms such as tremors, there is no treatment to halt the disease’s progression. Since the late 1990s, several drug companies have experimented with techniques to reduce levels of alpha-synuclein, the main component of protein clumps called Lewy bodies that are found in people with Parkinson’s. Affiris, based in Vienna, last year started the first clinical trial for a vaccine that lowers levels of alpha-synuclein.
The 32 patients enrolled in that trial may be at risk, says Demetrius Maraganore, author of a study that found the condition actually progressed more rapidly in patients with low levels of the protein. Maraganore, chairman of neurology at NorthShore University HealthSystem in Evanston, Ill., presented the study results on March 20 at the American Academy of Neurology meeting. “We may be saving a lot of patients from harm and pharmaceutical companies from wasting their money on a failed treatment strategy,” Maraganore said in an interview. Affiris did not respond to requests for comment regarding its trial.
The NorthShore study examined 1,098 Parkinson’s patients who had their DNA sequenced at the Mayo Clinic and were then contacted up to 15 years later. Those with a genetic variant that led to the lowest production of alpha-synuclein were 23 percent more likely to develop dementia or need a wheelchair than those whose bodies made more alpha-synuclein.
Earlier research found that people who were genetically programmed to make more of the protein had twice the risk of developing Parkinson’s—hence the push to design drugs that reduce alpha-synuclein levels. Once patients have the disease, however, making less of the protein seems to worsen the condition, Maraganore says. In a blog post about the study, Nate Herpich, associate director of research communications at the Michael J. Fox Foundation, wrote: “The reality is, the story surrounding alpha-synuclein is a complex one, and determining its role in Parkinson’s disease will require much more analysis.” As with other compounds in the body, the optimal amount of alpha-synuclein likely varies over time, says Maraganore: “It’s a protein that is probably critical for healthy nerve function, so that too little or too much at different points in time can be harmful.”