2024 Volume 41 Issue 5 Pages 735-739
The molecular basis and pathogenesis of Parkinson disease (PD) and related disorders have been elucidated by accumulated research, leading to the identification of potential therapeutic targets and the development of therapies. In 2023, foslevodopa/foscarbidopa subcutaneous injection, a new device–assisted therapy for PD, was marketed in Japan, providing a new therapeutic option for patients with advanced PD. In addition to symptomatic therapies, disease–modifying therapies that slow progression of the diseases are being developed around the world.
Here, we review papers published in 2023 on clinical trials, focusing primarily on randomized controlled trials (RCTs) on pharmacotherapy for PD. Results of RCTs on venglustat (GBA–related PD), ursodeoxycholic acid, buntanetap and transdermal nicotine have been reported as candidates for disease–modifying therapy. Venglustat and transdermal nicotine failed to demonstrate beneficial effects compared with placebo. Ursodeoxycholic acid and buntanetap showed some promise and need further investigation. Results of RCTs on focused ultrasound ablation of globus pallidus internus (GPi–FUSA) and Kw–6356 have been reported as candidates for symptomatic treatment of motor symptoms. GPi–FUSA met its primary endpoint, improving motor function and/or reducing dyskinesia at a higher rate than a sham procedure, but was associated with adverse events. Thus, longer and larger trials are required for further evaluation. Kw–6356 may be more effective than placebo for PD symptoms, but development has been halted. Results of RCTs on fecal microbiota transplantation (FMT), probiotics, SYN120, candesartan, clonidine, and sodium oxybate have been reported as candidates for symptomatic treatment of non–motor symptoms. FMT and probiotics significantly improved non–motor symptoms compared with placebo. SYN120 and candesartan failed to show beneficial effects on cognitive impairment, but might ameliorate apathy. Although the primary endpoint was not met, the results support further investigation of the effects of clonidine on impulse control disorders in PD and of oxybate on rapid–eye–movement sleep behavior disorder (RBD).
