Combination Disease-Modifying Therapy for Neurodegenerative Diseases Using Repurposed Drugs

Area of Science:

• Neuroscience
• Pharmacology
• Drug Discovery

Background:

• Neurodegenerative diseases (NDs) like Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD) represent a significant unmet medical need.
• Current therapeutic strategies for NDs are limited, necessitating novel approaches.

Purpose of the Study:

• To review the neuroprotective potential of existing drugs from various classes in preclinical models and human data for common NDs.
• To explore the concept of combinatory neuroprotective therapy using drug repurposing.
• To propose a strategy for designing ideal drug combinations to combat neurodegeneration.

Main Methods:

• Literature review of preclinical studies and published human data on drugs including chemical chaperones, GLP-1 RAs, iron chelators, and c-Abl TKIs.
• Conceptual analysis of drug repurposing for neuroprotection.
• Strategic proposal for combination therapy design.

Main Results:

• Several drug classes, including chemical chaperones, GLP-1 RAs, iron chelators, and c-Abl TKIs, demonstrate positive effects in preclinical models of NDs.
• Published human data suggest potential benefits of these repurposed drugs in individuals with PD, AD, ALS, and HD.
• Drug repurposing offers a viable strategy for developing combination therapies for NDs.

Conclusions:

• Existing drugs from diverse classes hold promise for treating neurodegenerative diseases.
• Combinatory neuroprotective therapy, leveraging drug repurposing, is a strategic approach to address the complexity of neurodegeneration.
• Designing ideal drug combinations targeting multiple pathogenic pathways is crucial for achieving clinically meaningful outcomes in NDs.