Potential Neuroprotective Therapy Ready for Next Stage of Development after Michael J. Fox Foundation Funding

New findings published in JAMA Neurology from research into a potentially protective therapy for Parkinson's disease (PD) show that with medical supervision, urate levels may safely be raised while mitigating risk of complications such as gout. Previous research showed that higher levels of the antioxidant urate were associated with lower risk and slower progression of PD.

In the Phase II Safety of Urate Elevation in Parkinson's Disease (SURE-PD) study -- led by Parkinson Study Group (PSG) investigators and funded by The Michael J. Fox Foundation for Parkinson's Research (MJFF) -- researchers found that oral ingestion of the urate precursor inosine is safe and tolerable and raises levels of urate in the blood and in the cerebrospinal fluid (CSF) bathing the brain.

SURE-PD grew out of results from two previous prospective studies that showed higher levels of urate in serum or cerebrospinal fluid at baseline predicted slower rates of Parkinson's progression, as measured clinically and with imaging technologies. Raising urate levels also was found to be neuroprotective in pre-clinical models of the disease.

PD patients should not self-medicate with inosine (which is commercially available), researchers warn, as it has not been proven as a therapy for Parkinson's and high doses can cause side effects such as gout and kidney stones and possibly high blood pressure. More research into inosine is needed to characterize the effect on Parkinson's and, if positive, define dosage and treatment regimens.

"We intend to find out whether inosine can be used as a protective therapy to delay Parkinson's in people at risk and slow disease progression in those already diagnosed," said lead investigator Michael Schwarzschild, MD, PhD, of Massachusetts General Hospital. "Such a disease-modifying therapy is a critical goal of PD research, and would greatly improve quality of life and prognosis for the millions living with this disease."

Schwarzschild also cites the potential of urate as a biomarker: a biological characteristic associated with the risk or presence of disease. Learning more about how urate levels present in different stages of Parkinson's can allow researchers to identify people at higher risk for PD, who may benefit from earlier intervention, and stratify clinical trials toward individuals with higher likelihood to respond to the treatment.

MJFF invested more than $5 million in SURE-PD in 2008, the Foundation's largest single grant at that time. Such early-stage funding is in line with MJFF's de-risking strategy meant to kick-start promising PD research projects and carry them to a stage attractive to other investors (e.g. pharmaceutical companies, private funders and/or the government).

While these results of the Phase II study set the stage for further development of inosine as a treatment for Parkinson's, industry interest may present a roadblock to drug development. Inosine is currently available as a supplement marketed for athletic performance improvement. This makes the compound less desirable for commercial investors whose business models rely on patenting and profiting from new drugs.

The PSG SURE-PD investigators call for "the development of a more definitive trial to investigate the ability of inosine treatment to slow clinical progression among persons with early PD who have lower urate." While they actively seek funding interest, patients wait for results.

"Research funding organizations can make a true difference in the lives of the millions by investing in promising disease-modifying treatments," said MJFF CEO Todd Sherer, PhD. "Inosine presents an opportunity to make significant strides toward our shared goal of a Parkinson's cure."

Listen to Schwarzschild discuss the study in a MJFF Parkinson's Podcast.