Huntingtons Disease and Tetrabenazine

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Huntingtons Disease and Tetrabenazine

• Nymol Ou

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What is HD?

• Autosomal dominant disease
• Causes a trinucleotide repeat expansion of a
  gene called Huntingtin (Htt), which results in
  high levels of the mutant Huntingtin (mHtt)
  protein
• Increased mHtt protein level induces
  deterioration of brain cells
• Results in loss of motor control and sensory
  reception

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Who is at risk?

• Its genetics!
• Both male and female are equally at risk
• Prevalence 5-8 people per 10,000
• Average onset age is between 35-40, but could
  start as early as 2 and as late as 80
• 10 affected is less than 20 years old

Figure 2 from Conneally article
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HD History

• Disease dates back to Middle Ages
• 1860 On of the first medical cases where
  symptoms of HD were examined (Johan Christian
  Lund)
• 1872 George Huntington defined disease and named
  it
• 1992 Anita Harding documented that the
  trinucleotide expansion played a role in the
  diseases mechanism
• 1993 Huntingtons Disease Collaborative Research
  Group isolated gene at 4p16.3.

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Diagnosis

• Physical examination
• Determine if movements are involuntary
• Psychological examination
• Check cognitive and emotional responses
• Blood test
• Since a positive blood test results in the person
  having HD, counseling sessions are required prior
  to test
• Usually do not test people under 18 unless they
  have strong symptoms
• Genetic testing
• Gene screening

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Effects of HD

• Causes involuntary movement
• Loss of intellect
• Isolates them socially
• Depression
• Speech impairment
• Anxiety
• Excessive weight loss

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Medical Treatments

• Since there is no cure for HD, we could only
  treat symptoms
• Three Option
• Medicinal treatment
• Tetrabenazine for chorea
• Antidepressants and antipsychotics
• Speech Therapy
• Gene Silencing
• Silencing gene should stop HD at its source
• Ongoing studies being done in labs

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Tetrabenazine

• Originally developed in 1950s to treat psychosis
• Now used to combat the chorea associated with HD
  by inhibiting the molecule vesicular monoamine
  transporter 2 (VMAT2)
• VMAT2 inhibition will decrease dopamine,
  serotonin, and nor epinephrine

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Mechanism
www.prestwickpharma.com/
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Whats on the Market Now?

• Nitoman (Canada) / Xenazine (New Zealand and
  Europe)
• Waiting for FDA approval for Xenazine in U.S.
• More clinical studies are needed before approval
  for market

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Xenazine

• www.cam-labs.com
• 25 mg tablets taken 3X a day
• Costs 249.99 per bottle (contains 112 tablets)
• Prestwick Pharmaceuticals Inc / Cambridge
  Laboratories

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Side Effects and How to Treat Them

• Depression - Monoamine oxidase inhibitors (MAOI )
• Drowsiness
• Neuroleptic malignant syndrome (NMS)-stop
  medication
• Hypotension
• Hypothermia

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Minocycline hydrochloride

• Currently used to treat acne and rosacea
• Possibly used for HD due to neuroprotective
  properties may inhibit 5- lipoxygenase
• Studies are being done as we speak

www.wikipedia.com
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