Zuranolone as an oral adjunct to treatment of Parkinsonian tremor: A phase 2, open-label study

• Published in: Journal of the neurological sciences 2021-02, Vol.421, p.117277-117277, Article 117277
• Main Authors: Bullock, Amy, Kaul, Inder, Li, Sigui, Silber, Christopher, Doherty, James, Kanes, Stephen J.
• Format: Article
• Language: English
• Subjects: Aged; GABAA receptor PAM; Humans; Parkinson Disease - complications; Parkinson Disease - drug therapy; Parkinson's; Pregnanes; Pyrazoles; Severity of Illness Index; Tremor; Tremor - drug therapy; Tremor - etiology; Zuranolone
• ISSN: 0022-510X; 1878-5883
• DOI: 10.1016/j.jns.2020.117277

Parkinson's disease (PD) is characterized by both motor and nonmotor deficits. Among cardinal symptoms of this disorder, tremor is the least responsive to dopamine replacement therapy and is often undertreated. Zuranolone (SAGE-217) is an investigational oral neuroactive steroid (NAS) gamma-aminobutyric acid A (GABAA) receptor–positive allosteric modulator (PAM) that has been investigated for its safety and efficacy in patients with PD. In the current open-label study, zuranolone capsules (20 to 30 mg) were administered for 7 days in 14 patients (mean age, 65.1 years; mean time since PD diagnosis, 9 years). The primary efficacy endpoint was reduction in tremor symptoms, as assessed by change from baseline in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II/III Tremor Scores on Day 8. Additional endpoints included improvements in overall motor symptoms, and motor and nonmotor aspects of daily living. Adverse events (AEs) were also monitored. The MDS-UPDRS Part II/III Tremor Score improved by 40% (P