Urate-Elevating Inosine does not slow progression of Parkinson disease, finds JAMA study

In a study conducted by Dr. Michael A. Schwarzschild and colleagues, it was found that treatment with Urate-elevating inosine treatment was not clinically beneficial in early Parkinson disease, compared to placebo.It  didn't result in  significant difference in the rate of clinical disease progression among Parkinson's disease (PD) patients. The findings of this study were published in The Journal of the American Medical Association on 14th September, 2021.

Despite its links to crystallopathic, cardiovascular, and metabolic problems, urea elevation has been investigated as a potential disease-modifying approach for Parkinson disease (PD) based on convergent molecular, epidemiological, and clinical evidence. This led the researchers to investigate if long-term urate-elevating therapy with the urate precursor inosine slows the development of early Parkinson's disease.

Oral inosine therapy in early Parkinson's disease was studied in a placebo-controlled phase 3 study. A total of 587 people agreed to participate, and 298 people with Parkinson's disease who did not yet require dopaminergic medication, striatal dopamine transporter deficiency, and serum urate concentrations less than the population median (5.8 mg/dL) were randomized between August 2016 and December 2017 at 58 US sites and were followed up on until June 2019.

In this randomized clinical trial that included 298 participants with early Parkinson disease, the rate of clinical disease progression as measured by the Movement Disorder Society Unified Parkinson Disease Rating Scale (parts I-III) total score prior to initiation of dopaminergic medication was 11.1 points per year in the inosine group and 9.9 points per year in the placebo group, a difference that was not statistically significant.

Over a two-year period, no substantial improvement from inosine was shown in any secondary clinical measure of Parkinson's disease or in a dopamine transporter imaging biomarker of nigrostriatal dopaminergic cell loss.

Despite preclinical data in cellular and animal models of PD, the results of this research do not support a protective effect of urate as the foundation of the repeatable epidemiological association between increased urate and decreased risk and development of PD. The study concludes by pointing out that the findings doesn't support the use of inosine as a treatment for early PD.

Reference:

Bluett, B., Togasaki, D. M., Mihaila, D., Evatt, M., Rezak, M., Jain, S., Schwarzschild, M. A., Ascherio, A., Casaceli, C., Curhan, G. C., Fitzgerald, R., Kamp, C., Lungu, C., Macklin, E. A., Marek, K., Mozaffarian, D., Oakes, D., Rudolph, A., … Mestre, T. (2021). Effect of Urate-Elevating Inosine on Early Parkinson Disease Progression. JAMA, 326(10), 926. https://doi.org/10.1001/jama.2021.10207