Huntington's Disease

Neuroscience II

Kate Sears

History & Prevalence

• First described by George Huntington in 1872
• Huntington Chorea 
• San Luis in Venezuela was discovered by Amerigo Negrette
• Today, 1 in 10,000 have HD
• 250,000 at risk

Symptoms

• Two types: Adult and Juvenile (differ genetically)
• Neurodegenerative: mental processes and physical control
• Psychological symptoms 
• Physical symptoms
• Fate

Neurobiology

Basics:

• Nerve Cells
• Basal Ganglia
• Direct pathways
• Indirect pathways
• GABA

Genetics

Autosomal Dominant

50% hereditary rate 

Chromosome 4

Repetition of CAG

• Normal: 10-28
• At risk: 29-35
• Adult onset: 36-45
• Juvenile onset: 70-120

The Gene

• 20+ years to isolate
• Not a common mutation
• Discovered in 1993
• Isolated IT-15 (Interesting Transcript)
• Repetition of CAG: Glutamine

The Protein

• Huntingtin Protein
• Codes for p53 
• Halts progression of cell cycle
• Adding glutamine increases levels
• Tumor Suppressor 

Theories?

• HIP-1 and HAP-1 

• Mitochondria of striatal cells

• Excitatory?

In Summary

http://www.nature.com/nm/journal/v6/n11/fig_tab/nm1100_1208_F1.html

Research

http://www.hdsa.org/research/therapies-in-pipeline.html

Tetrabenazine

• Treatment for Chorea in 2008
• 1st FDA Approved Drug
• Dopamine depleter
• Serotonin and norepinephrine

Therapies

• Physical Therapy
• Psychotropic
• Tetrabenazine

Future?

• Genetic testing

• HIP-1 and HAP-1

• Glutamate

• p53 

• Pathways

Questions?