Why is it so difficult to discover drugs for amyotrophic lateral sclerosis? A protein intrinsic disorder perspective - PubMed
8 hours ago
- #Amyotrophic Lateral Sclerosis
- #Drug Discovery
- #Intrinsically Disordered Proteins
- ALS is considered a spectrum disorder with significant person-to-person variability due to genetic and environmental factors, making a single 'magic bullet' drug unlikely.
- Drug discovery for ALS faces a 95% failure rate due to genetic complexity, lack of sensitive biomarkers, diagnostic delays, inadequate animal models, and poor clinical trial design.
- The article highlights the prevalence of intrinsic disorder in ALS-related proteins, which hinders rational structure-based drug discovery by overlooking intrinsically disordered proteins (IDPs).
- IDPs play crucial roles in neurodegeneration and ALS pathology, and ignoring these 'shapeshifters' contributes to the ineffectiveness of a 'one-size-fits-all' approach.
- To improve drug discovery success for ALS, the article suggests shifting from structure-based models to intrinsic disorder-centric approaches.