Large animal models for Huntington's disease research

Area of Science:

• Neuroscience
• Genetics
• Animal Modeling

Background:

• Huntington's disease (HD) is an inherited neurodegenerative disorder with no current cure.
• The disease is caused by expanded CAG repeats in the huntingtin (HTT) gene, leading to protein misfolding and aggregation in the brain.
• Rodent models have limitations; thus, large animal models are vital for understanding HD pathogenesis and therapeutic development.

Purpose of the Study:

• To provide a comprehensive overview of large animal models for Huntington's disease research.
• To highlight recent advancements in establishing HD knock-in (KI) pigs and their genetic therapy.
• To explore the application of sheep, non-human primates, and pigs in investigating and treating neurodegenerative disorders.

Main Methods:

• Review of existing literature on large animal models for HD.
• Inclusion of recent findings on HD knock-in pig models and genetic therapies.
• Focus on the utility of sheep, non-human primates, and pigs in HD research.

Main Results:

• Large animal models, including pigs, sheep, and NHPs, offer significant advantages over rodent models for studying HD.
• Sophisticated models now exist that accurately replicate HD pathology.
• Recent progress includes the development of HD knock-in pigs and advancements in their genetic therapy.

Conclusions:

• Large animal models are indispensable for advancing Huntington's disease research.
• These models facilitate the discovery of novel therapeutic targets and improve drug delivery strategies.
• Continued development and utilization of large animal models are essential for effective treatment of neurodegenerative disorders like HD.