Advances in Pharmacotherapy for Neurodegenerative Disorders: From Mechanisms to Clinical Trials

Abstract

Neurodegenerative disorders (NDs), such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, Huntington’s disease, and multiple sclerosis, are progressive conditions with complex pathophysiology involving protein aggregation, oxidative stress, neuroinflammation, and mitochondrial dysfunction. Current pharmacotherapies primarily offer symptomatic relief, with limited success in modifying disease progression. However, recent advances have introduced promising strategies, including neuroprotective
agents, immunomodulatory therapies, gene and RNA-based interventions, and small-molecule inhibitors targeting protein misfolding. AI-driven drug discovery is revolutionizing therapeutic development, while biomarker-guided precision medicine enhances patient stratification and treatment efficacy. Additionally, advancements in stem cell-based therapies and regenerative medicine offer new hope for restoring neuronal function and slowing disease progression. Innovative clinical trial designs, such as adaptive and biomarker-based approaches, are improving the evaluation of novel therapies, increasing their likelihood of clinical success. Despite these advancements, challenges such as blood-brain barrier limitations, drug resistance, patient heterogeneity, and lengthy trial durations continue to hinder progress. Further, the high costs of drug development and regulatory complexities present additional obstacles to bringing novel therapies to market. Future research must focus on overcoming these barriers through multi-omics integration, personalized medicine, AI-driven analytics, and advanced drug delivery systems to develop effective disease-modifying treatments, enhance therapeutic accessibility, and improve long-term patient outcomes.