Objective/Rationale: 

Urate – a natural metabolite and major antioxidant in humans – is emerging as the first molecular predictor of both the risk and the progression of typical Parkinson’s disease (PD). Studies of healthy individuals have linked urate levels in the upper normal range to a reduced risk of developing PD. Similarly, studies of individuals recently diagnosed with PD have found that the disease tends to progress more slowly in those with higher urate levels in their blood and cerebrospinal fluid, the fluid that surrounds the brain. The findings raise the possibility that boosting brain urate by treatment with the urate precursor inosine could slow the brain cell degeneration of PD. Before embarking on a neuroprotection trial of inosine for PD, careful assessment of the safety, validity and methodology of this approach is warranted. 

Project Description:

Pending federal regulatory approval, ninety subjects with recently diagnosed PD will be enrolled in a randomized, double-blinded clinical trial of inosine. The study will determine whether and at what dose inosine can safely elevate levels of urate in the fluid around the brain. Subjects will take capsules containing inosine or placebo in combinations designed to produce no, mild or moderate elevation of urate. Because kidney stones and gout are known risks and cardiovascular disease is a possible risk of higher urate levels, safety measures will be in place to help avoid these conditions, and to detect and treat them should they arise. Three months after enrollment cerebrospinal fluid will be tested for urate levels. If a tolerable dose of inosine adequately increases urate in the cerebrospinal fluid then subjects would continue on treatment for up to two years to assess long-term safety. 

Relevance to Treatment of Parkinson’s Disease/ Anticipated Outcome: 

The identification of urate as an unprecedented predictor of better outcomes in Parkinson’s disease has encouraged consideration of its precursor inosine as a potential neuroprotectant in PD. This LEAPS project would shorten substantially the lead time to develop a full neuroprotection trial, and through optimization of key design features would considerably enhance the likelihood of its safety and success.