Emerging therapies in hereditary ataxias

Area of Science:

• Neuroscience
• Genetics
• Pharmacology

Background:

• Hereditary ataxias (HAs) involve complex genetic mechanisms, including RNA and protein level dysfunctions.
• Preclinical research is advancing therapeutic strategies for various HAs.

Purpose of the Study:

• To review current translational research for Friedreich ataxia (FRDA) and polyglutamine ataxias.
• To highlight the progress and challenges in developing effective treatments for these rare neurological disorders.

Main Methods:

• Gene editing, gene/protein replacement, and gene knockdown strategies are being investigated.
• Therapeutic delivery methods include viral vectors, oligonucleotides, cell-penetrating peptides, and synthetic transcription factors.

Main Results:

• Understanding of HA pathophysiology has improved, revealing loss-of-function and gain-of-function mechanisms.
• Diverse preclinical therapeutic approaches show potential for treating HAs.

Conclusions:

• Translational research for FRDA and polyglutamine ataxias is active but requires further development.
• Identifying safe molecules, optimizing delivery, and conducting innovative clinical trials are crucial next steps.