Lecture on Huntington's Disease and Gene Therapy

Overview of Huntington's Disease

• Genetic Brain Disorder: Huntington's disease is caused by mutations in the huntingtin (HTT) gene.
• Effects: Progressive breakdown of nerve cells in the brain affecting movement, mood, and cognition.
• Gene Function: The precise function of the HTT gene in healthy adults is not fully understood.
• Mutation Impact: The mutation causes the production of toxic proteins leading to neuron death.
• Impact on Families: Loss of independence, emotional strain on caretakers, and genetic transmission risk (50% chance).

Current Research and Hope in Gene Therapy

• No Cure or Effective Treatment: Currently, no cure or highly effective treatments exist.
• Gene Therapy Potential: Aims to alter cellular protein production by replacing missing or abnormal genes.
• Objective in Huntington's: Lower production of toxic HTT protein to slow neuronal breakdown.

Clinical Trial Approaches

Micro RNAs (miRNAs)

• Function: Short RNA molecules reducing specific protein production.
• Mechanism: Bind to messenger RNA (mRNA) to prevent protein synthesis.
• Gene Therapy Use: Insert miRNAs to inhibit mutant HTT protein production.
• Delivery Method: Delivered into cells using viral vectors, which are engineered to be non-pathogenic and therapeutic.
• Administration: Typically aimed as a one-time treatment.

Antisense Oligonucleotides (ASOs)

• Function: Anti-sense therapy modifying gene expression.
• Mechanism: Synthetic DNA/RNA mimics bind to faulty HTT gene, blocking harmful protein production.
• Administration: Generally requires multiple doses over time.

Research and Future Prospects

• Ongoing Trials: Research continues optimistically to find safe, effective treatments.
• Resources: Further information and resources are available at ASGCT.org.

These notes summarize the key points from a lecture on the genetic disorder Huntington's disease, its impact, and the potential of gene therapy in its treatment.