Cell and gene therapy for amyotrophic lateral sclerosis

Area of Science:

• Neuroscience
• Genetics
• Biotechnology

Background:

• Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive muscle weakness and cognitive deficits.
• Genetic factors account for only about 10% of ALS cases, complicating the identification of therapeutic targets due to complex genotype-phenotype relationships.
• Heterogeneity in disease mechanisms and affected cell types, beyond motor neurons, presents significant challenges for therapeutic development.

Purpose of the Study:

• To review the current landscape of human preclinical models used in ALS research.
• To examine recent advancements in cell and gene therapy approaches for ALS.
• To provide an overview of strategies supporting clinical trials for ALS.

Main Methods:

• Review of biotechnologic techniques, cell and RNA engineering.
• Analysis of animal models and patient-specific human stem cell and organoid models.
• Assessment of current clinical cell and gene therapy strategies.

Main Results:

• Significant progress has been made in developing advanced preclinical models, including stem cell and organoid systems.
• Biotechnological advancements have accelerated mechanistic and therapeutic discoveries in ALS.
• The number of ongoing clinical trials for ALS is increasing, reflecting progress in the field.

Conclusions:

• Human preclinical models are crucial for supporting and refining ALS clinical trial strategies.
• Cell and gene therapies represent promising avenues for future ALS treatment development.
• Continued research and technological innovation are vital for overcoming the challenges in treating ALS.