Huntington's Disease Huntington's Chorea

1. Ade Wijaya, MD – November 2019

2. Autosomal dominant
Progressive
Neurodegenerative
5–10 per 100,000 in the Caucasian population
Roos RAC. Huntington’s disease: a clinical review. Orphanet J Rare Dis. 2010;5:40.
Mestre T, Ferreira J, Coelho MM, Rosa M, Sampaio C. Therapeutic interventions for symptomatic treatment in Huntington’s disease. Cochrane Database Syst Rev.
2009;(3):CD006456.

3. Cytosine-adenine-guanine (CAG) trinucleotide
repeat expansion in the huntingtin protein
located on chromosome 4p16.3
Cell toxicity and dysfunction of neurons
Striatal and cortical atrophy
Coppen, E. M., & Roos, R. A. (2017). Current pharmacological approaches to reduce chorea in Huntington’s disease. Drugs, 77(1), 29-46.

4. Increasingly severe motor disturbances,
cognitive impairment, and psychiatric
symptoms
The mean age of disease onset is between 30
and 50 years (ranging from 2 to 85 years),
with the mean duration of the disease
between 17 to 20 years
van Duijn E, Craufurd D, Hubers AAM, Giltay EJ, Bonelli R, Rickards H, et al. Neuropsychiatric symptoms in a European Huntington’s disease cohort (REGISTRY). J
Neurol Neurosurg Psychiatry. 2014;85:1411–8.
Roos RAC. Huntington’s disease: a clinical review. Orphanet J Rare Dis. 2010;5:40.

5. motor
psychiatricneurobehavior
Roos RAC. Huntington’s disease: a clinical review. Orphanet J Rare Dis. 2010;5:40.
van Duijn E, Craufurd D, Hubers AAM, Giltay EJ, Bonelli R, Rickards H, et al. Neuropsychiatric symptoms in a European Huntington’s disease cohort (REGISTRY). J
Neurol Neurosurg Psychiatry. 2014;85:1411–8.

6.  Cognitive impairment Progrssive working
memory, executive dysfunction, and attention
deficits.
 Behavioral and psychiatric symptoms in HD
include apathy, depression, irritability and
aggression, and obsessive-compulsive
behavior
 Involuntary movements such as chorea,
dystonia, and tics, and impairments in
voluntary movements such as hypokinesia,
apraxia, and motor impersistence
Paulsen JS. Cognitive impairment in Huntington disease: diagnosis and treatment. Curr Neurol Neurosci Rep. 2011;11:474–83.
Roos RAC. Clinical neurology. In: Bates G, Tabrizi S, Jones L, editors. Huntington’s dis. 4th ed. Oxford: Oxford University Press; 2014. p. 25–35.
van Duijn E, Craufurd D, Hubers AAM, Giltay EJ, Bonelli R, Rickards H, et al. Neuropsychiatric symptoms in a European Huntington’s disease cohort (REGISTRY). J
Neurol Neurosurg Psychiatry. 2014;85:1411–8.

7.  Striatal atrophy
 Abnormal neurotransmission of the
dopamine, glutamate, and gamma-amino
butyric acid (GABA) systems
 Postsynaptic dopaminergic dysfunction of
dopaminergic type 1 (D1) and type 2 (D2)
receptors in the striatum
 Choreiform movements: overstimulation of
dopamine receptors
Coppen, E. M., & Roos, R. A. (2017). Current pharmacological approaches to reduce chorea in Huntington’s disease. Drugs, 77(1), 29-46.

8.  Tetrabenazine (FDA approved)
 Dopamine antagonists: tiapride, clozapine,
olanzapine, risperidone, quetiapine
 Anti-glutamanergics: amantadine, riluzole
 Aripiprazole
 Benzodiazepines (such as clonazepam and
diazepam), haloperidol, and sulpiride
 Potential New Treatment Options:
Deutetrabenazine, pridopidine
Coppen, E. M., & Roos, R. A. (2017). Current pharmacological approaches to reduce chorea in Huntington’s disease. Drugs, 77(1), 29-46.

9.  Autosomal dominant, progressive,
neurodegenerative disease
 Cortical and striatal atrophy
 Motoric (choreiform movements),
neurobehavior, and psychiatric symptoms
 Tetrabenazine is the only drug approved by
the US FDA for the treatment of chorea in
Huntington’s disease