Recent advances in amyotrophic lateral sclerosis research: perspectives for personalized clinical application

Area of Science:

• Neuroscience
• Pharmacology
• Genetics

Background:

• Amyotrophic lateral sclerosis (ALS) lacks effective treatments that impede disease progression.
• Existing symptomatic drugs offer limited relief and do not alter the disease course.
• Numerous preclinical agents have failed translation to human therapies due to pharmacokinetic, delivery, or model limitations.

Purpose of the Study:

• To review novel pharmacological approaches for amyotrophic lateral sclerosis (ALS) treatment.
• To highlight the need for multi-target therapies addressing ALS's complex pathology.
• To discuss personalized treatment strategies considering risk factors, biomarkers, and clinical heterogeneity.

Main Methods:

• Literature review of preclinical and clinical studies on ALS therapeutics.
• Analysis of emerging treatment modalities including multimodal compounds, genetic manipulation, and cell-based therapies.
• Discussion of challenges in translating preclinical findings to patient care.

Main Results:

• Over 150 therapeutic agents have been tested in preclinical ALS models with limited success.
• Significant differences exist between murine ALS models and human disease, hindering translation.
• Multi-target approaches are crucial due to the complex and multifactorial nature of ALS pathology.

Conclusions:

• Future ALS therapies must address multiple pathological pathways simultaneously.
• Personalized medicine approaches, considering patient-specific factors, are essential for effective ALS management.
• Novel strategies like iron-binding compounds, gene therapy, and cell-based treatments show promise for advancing ALS care.