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Disease Modification in Parkinson's Disease: Current Approaches, Challenges, and Future Considerations
Anthony E Lang1, Alberto J Espay2
1Edmond J. Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, UHN, Division of Neurology, University of Toronto, Toronto, Ontario, Canada.
Summary
Developing disease-modifying treatments for Parkinson's disease (PD) remains a challenge. This review explores current strategies targeting alpha-synuclein, distinct pathogenic mechanisms, genetic subtypes, and other interventions, highlighting the need for personalized approaches.
Area of Science:
- Neuroscience
- Neurology
- Pharmacology
Background:
- Parkinson's disease (PD) lacks treatments that slow neurodegeneration.
- Past attempts at disease-modifying therapies have been unsuccessful.
- Understanding PD pathogenesis and patient heterogeneity is crucial.
Purpose of the Study:
- To review disease modification strategies for Parkinson's disease.
- To discuss challenges and current treatment approaches.
- To highlight future research directions and outstanding questions.
Main Methods:
- Review of existing literature on PD pathogenesis and therapeutic strategies.
- Categorization of treatments into four main areas: α-synuclein, distinct pathogenic mechanisms, genetic subtypes, and other interventions.
- Emphasis on treatments currently in clinical development.
Main Results:
- Multiple therapeutic avenues are under investigation, including targeting α-synuclein, oxidative stress, and genetic factors.
- Current clinical trials are evaluating interventions like inosine, isradipine, deferiprone, and passive immunization.
- Significant challenges remain in understanding disease heterogeneity and identifying optimal therapeutic targets.
Conclusions:
- Effective disease modification in PD requires a deeper understanding of individual patient pathways.
- Future therapies may involve personalized or combination approaches ('cocktails').
- Enriching clinical trial populations for specific pathogenic processes is essential to avoid past failures.