Clinical Trial Considers Inosine Safe and May Lead to Future Treatments to Slow the Progression of PARKINSON’S DISEASE
Michael Schwarzschild, M.D., Ph.D. who is connected to the Harvard School of Public Health and Massachusetts General Hospital has been conducting research with urate levels for many years. In a report issued in May 2012, he stated that they had rather unexpectedly found that people who had higher levels of urate (uric acid) also had a lower than average chance of developing PARKINSON’S DISEASE. In that study, they found that urate served as an antioxidant that could protect cells from cell death, however it required the assistance or cooperation of neighboring cells, called astrocytes. Astrocytes are cells that provide both structural and metabolic support to neurons and it is their intervention that determines how the urate is used within the neural cells. The next question was to find out if urate increased artificially would provide the same protection as urate produced naturally.
The results of that study have found that Inosine, a precursor to uric acid, could be added to increase urate and that the results were safe and tolerable. To accomplish this they enrolled 75 very early onset people with PARKINSON’S DISEASE who had not yet begun taking any dopamine replacement therapy and who also had very low levels of urate in a two year study. Inosine occurs naturally in the human system, as a product of normal metabolism. Inosine given in this study was in pill form, which meant it had to be broken down via the digestive system. Two well known side effects of high uric acid levels are gout and kidney stones, so these potential effects were carefully monitored during the study. While kidney stones were developed in three of the participants, in two of the participants they were not related to the levels of urate and all were resolved successfully. After six months in the study, 95 per cent of the participants had no difficulties taking the Inosine drug.
The strengths of Inosine tested on these participants showed an increase in urate levels in both blood and cerebrospinal fluids. One month after stopping the medication, the urate levels of all participants returned to their pre-study levels. The safety and tolerability data together with some early data on effectiveness looks very encouraging “These results support advancing to a larger trial capable of addressing whether Inosine might fill the critical unmet need for a disease-modifying treatment.” says Dr. Schwarzschild. He and fellow investigators are moving toward the development of a much larger phase 3 trials which will study specifically the benefits and effectiveness of Inosine.
Urate levels increased artificially could have potentially serious side effects, so Inosine is not yet considered a safe treatment for PARKINSON’S DISEASE. “We know that excessively high urate can lead to kidney stones, gout and possibly other untoward effects, which is why attempts to elevate urate are best pursued in carefully designed clinical trials where the risks can be reduced and balanced against possible benefits, ” cautions Dr. Schwarzschild.
Michael A. Schwarzschild, MD, PhD; Alberto Ascherio, MD, DrPH; M. Flint Beal, MD; Merit E. Cudkowicz, MD; Gary C. Curhan, MD; Joshua M. Hare, MD; D. Craig Hooper, PhD; Karl D. Kieburtz, MD; Eric A. Macklin, PhD; David Oakes, PhD; Alice Rudolph, PhD; Ira Shoulson, MD; Marsha K. Tennis, RN; Alberto J. Espay, MD, MSc; Maureen Gartner, RN, MEd; Albert Hung, MD, PhD; Grace Bwala, MBBS; Richard Lenehan, MD; Elmyra Encarnacion, MD; Melissa Ainslie; Richard Castillo; Daniel Togasaki, MD, PhD; Gina Barles; Joseph H. Friedman, MD; Lisa Niles, MS; Julie H. Carter, RN, MN, ANP; Megan Murray, MA; Christopher G. Goetz, MD; Jeana Jaglin, RN, CCRC; Anwar Ahmed, MD; David S. Russell, MD, PhD; Candace Cotto, RN; John L. Goudreau, DO, PhD; Doozie Russell; Sotirios Andreas Parashos, MD, PhD; Patricia Ede, RN; Marie H. Saint-Hilaire, MD; Cathi-Ann Thomas, RN, MS; Raymond James; Mark A. Stacy, MD; Julia Johnson, MD; Lisa Gauger, BA; J. Antonelle de Marcaida, MD; Sheila Thurlow, MSN, BSN; Stuart H. Isaacson, MD; Lisbeth Carvajal; Jayaraman Rao, MD; Maureen Cook, RN, BSN; Charlise Hope-Porche, RN; Lauren McClurg; Daniela L. Grasso; Robert Logan, MS; Constance Orme, BA; Tori Ross; Alicia F. D. Brocht; Radu Constantinescu, MD; Saloni Sharma, MBBS; Charles Venuto, PharmD; Joseph Weber; Ken Eaton. Inosine to Increase Serum and Cerebrospinal Fluid Urate in Parkinson Disease: A Randomized Clinical Trial. JAMA Neurology, December 2013
Review by Marcia McCall