Combination Disease-Modifying Therapy for Neurodegenerative Diseases Using Repurposed Drugs.

Abstract

We review the positive effects of several existing drugs from different classes, such as chemical chaperones, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), iron chelators, and cluster-Abelson tyrosine kinase inhibitors (c-Abl TKIs), in preclinical disease models and in available published human data following use of these drugs in individuals with common neurodegenerative diseases (NDs), including Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD). A concept of combinatory neuroprotective therapy using a drug-repurposing approach is then discussed. Finally, we propose a strategy to design an ideal combination of drugs able to address multiple pathogenic processes involved in neurodegeneration to achieve clinically meaningful results. ANN NEUROL 2026 ANN NEUROL 2026;99:1099-1112.