Inosine may not slow early progression of Parkinson’s disease in phase 3 study

According to study results published in JAMA, uric acid-increasing inosine treatment had no positive effect on the rate of clinical disease progression in patients with newly diagnosed Parkinson’s disease (PD).

Previous studies have shown that urate, the major antioxidant circulating in human plasma, may play a role in disease progression in patients with Parkinson’s disease, leading to a phase 2 study of oral inosine, a metabolic precursor to urate, which has proven to be safe and tolerable. The aim of the current phase 3 study was to investigate the influence of inosine on the course of the disease in patients with early-stage Parkinson’s disease.

The randomized, double-blind, placebo-controlled study enrolled 298 patients with Parkinson’s disease from 58 US locations. Study participants were randomized to receive inosine (149 patients) or placebo (149 patients).

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The primary endpoint was the rate of clinical progression in early Parkinson’s disease at 2 years according to the rate of change in the total score of the movement disorder society Unified Parkinson Disease Rating Scale (MDS-UPDRS; Parts I-III) prior to initiation of dopaminergic drug therapy.

In September 2018, the Data and Safety Monitoring Panel reviewed the second pre-determined, non-binding interim analysis for premature discontinuation due to the effectiveness or futility of the inosine treatment, and since the results met the pre-determined criterion for futility, the study was rated 273 (92% ) completed early. ) of the randomized participants (49% women; mean age 63 years) who completed the study.

The absolute change from baseline in serum urea was 2.03 milligrams per deciliter in the inosine group compared to an absolute change of 0.01 milligrams per deciliter in the placebo group (P <0.001).

Clinical progression of Parkinson’s disease was not slowed by long-term treatment with oral inosine dosed to increase serum urea, as the rate of change in MDS-UPDRS Part I-III scores in patients receiving inosine was 11.1 Points per year was compared with 9.9 points per year among those in the placebo group (P = .18).

Similarly, no significant benefit of inosine was seen in a secondary clinical measurement of PD or in an imaging biomarker of the dopamine transporter for nigrostriatal dopaminergic neuron loss over 2 years.

Serious adverse events were more common in the placebo group (13.1 vs. 7.4 per 100 patient-years), but kidney stones were more common in inosine-treated patients (1.4 vs. 7.0 stones per 100 patient-years) ).

The study had several limitations, including a potentially beneficial effect of urate in patients with previous or prolonged PD exposure and the inability to rule out a potential benefit in a subset of patients with PD.

“In patients recently diagnosed with PD, treatment with inosine compared to placebo did not result in a significant difference in the rate of clinical disease progression. The results do not support the use of inosine to treat early-stage Parkinson’s, the researchers concluded.

Disclosure: Some study authors stated links with biotech, pharmaceutical, and / or device companies. For a full list of the author’s disclosures, see the original reference.


Parkinson’s Study Group SURE-PD3 investigators. Effect of urate-increasing inosine on early progression of Parkinson’s disease: the randomized clinical trial SURE-PD3. JAMA. Published online September 14, 2021. doi: 10.1001 / jama.2021.10207

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