Fluctuations in Parkinson's disease: progress and challenges

Introduced in the 1960s, dopamine replacement therapy with levodopa remains the cornerstone of management for individuals with Parkinson's disease. 1 Foltynie T Bruno V Fox S Kühn AA Lindop F Lees AJ Medical, surgical, and physical treatments for Parkinson's disease. Lancet. 2024; 403: 305-324 Summary Full Text Full Text PDF Google Scholar Patients on levodopa often have treatment-related complications, such as fluctuations and dyskinesia. Early data estimated that, for each year of exposure to levodopa, about 10% of people with Parkinson's disease develop fluctuations and dyskinesia. 2 Aradi SD Hauser RA Medical management and prevention of motor complications in Parkinson's disease. Neurotherapeutics. 2020; 17: 1339-1365 Summary Full Text Full Text PDF PubMed Scopus (0) Google Scholar In a prospective follow-up study over 10 years, 254 (35%) of 734 patients developed fluctuations. 3 Kelly MJ Lawton MA Baig F et al. Predictors of motor complications in early Parkinson's disease: a prospective cohort study. Mov Disord. 2019; 34: 1174-1183 Crossref PubMed Scopus (40) Google Scholar Regardless of the precise numbers, fluctuations are a source of disability for many individuals with Parkinson's disease. Safety and efficacy of continuous subcutaneous levodopa–carbidopa infusion (ND0612) for Parkinson's disease with motor fluctuations (BouNDless): a phase 3, randomised, double-blind, double-dummy, multicentre trialResults of this phase 3 study showed that subcutaneous ND0612 used in combination with oral immediate-release levodopa–carbidopa increased on time without troublesome dyskinesia and reduced off time, with a favourable benefit–risk profile. ND0612 might offer a safe and efficacious subcutaneous levodopa infusion approach to managing motor fluctuations in people with Parkinson's disease. The ongoing open-label extension phase will provide further information on the long-term efficacy and safety of treatment. Full-Text PDF