Istradefylline/L‐DOPA Parkinson's disease therapy and energy coupling

Both dopamine and adenosine are physiologically involved in cellular energy metabolism.Novel approaches targeting delaying progression strategies for Parkinson's disease (PD) examined the effects of long‐term use of A2AR antagonist/istradefylline (IST) adjunct to L‐DOPA (LD), nutshell IST‐LD, with an expected energy coupling (EC) to attenuate neuronal excitotoxicity.A single‐center prospective open cohort study was conducted at the Department of Neurology, Okinawa Islands, Japan. The cohort included incident and prevalent PD cases that were non‐randomly assigned to the IST‐LD (n = 90) and LD (n = 157) groups, followed by an open‐label treatment in clinical practice from October 2013 to September 2020. Patients were evaluated using physician‐rated MDS‐UPDRS I/III, and patient‐rated MDS‐NMS using the total score, body weight, and blood biomarkers of EC.As the primary clinical outcome, MDS‐UPDRS part III scores showed less worsening in the IST‐LD than in the LD group (1.29 ± 6.0 vs. 5.0 ± 6.5, p < 0.01) and off‐time Hoehn and Yahr stage (0.05 ± 0.49 vs. 0.26 ± 0.54, p < 0.01). As the secondary clinical outcome, the detected mean body weight losses were similar between the two groups; however, the evident linkage of the daily dose of LD and variations in the blood markers of IGF‐I and HKII, which were inferred as LD‐mediated energy demand effects, were partially attenuated by IST.IST‐LD plays an essential role in behavioral outputs for patients with PD and might contribute to the interplay of energy‐consuming demands of LD with the attenuation of weight loss and emerging type 2 diabetes mellitus.