Next-generation pharmacological strategies for Parkinson's disease: a systematic literature review of symptom management and disease modification.

Parkinson disease is an ongoing neurodegenerative disorder, and both motor and non-motor symptoms are involved with the existing therapies having minimal effects on the disease but only symptom alleviation. The goal of this systematic literature review was to generalize up-to-date evidence on the next-generation pharmacological strategies to manage the symptoms and the disease in a patient with Parkinson disease. The review was based on PRISMA 2020 and included the analysis of peer-reviewed studies of human research published in 2015-2026 and retrieved in the key databases, such as PubMed, Scopus, Web of Science, and Cochrane Library. This included 30 eligible studies consisting of randomized studies, observational studies, and early clinical trials. The results show that, although dopaminergic treatment continues to play a central role in managing motor symptoms, new methods such as gene therapy, gene editing, stem cell-based regeneration, nanomedicine delivery systems, repurposed drugs, artificial intelligence-based precision medicine approaches have a good neuroprotective and disease-modifying potential. Nonetheless, the majority of new interventions are still in preclinical or first line clinical phase, with a defined subset of emerging gene-, cell-, and nanotechnology-based approaches evaluated only in animal or in-vitro models rather than in PD patients and associated with small sample size, invasive delivery, limited follow-up and lack of long-term safety information. In general, the review concludes by stating that there has been significant advancement in diversification of therapeutic targets and mechanisms, but rigorous large-scale biomarker-directed clinical trials are needed to translate these advances to effective and sustainable treatment of the Parkinson disease.