Huntington's Disease Flashcards
Genetically, describe Huntington’s disease.
Huntington’s disease is an autosomal dominant hereditary disorder.
What is the prevalence of Huntington’s disease?
1 in 10-20,000.
What is the average age of presentation of Huntington’s disease?
35-42 years.
Over how long does Huntington’s disease progress?
10-25 years.
What are the symptoms of Huntington’s disease?
• Involuntary, rapid, jerky movements affecting the
face, arms, legs, and trunk.
• Gradual loss of thought processing and acquired
intellectual abilities (dementia).
• Impairment of memory, abstract thinking, and
judgement.
• Disorientation – improper perceptions of time,
place, or identity.
• Personality changes.
• Agitation.
• Slurred speech.
• Difficulty swallowing – aspiration.
What is the pathology of Huntington’s disease?
Huntington’s is characterised by generalised shrinkage and thinning of the cortex of affected patient’s brains. Early motor symptoms are due to a loss of GABA/enkephalin containing medium spiny neurones of the striatum (D2 receptor-containing). As the disease progresses there is the loss of the whole nigrostriatal projection.
Dementia and psychiatric problems are due to a loss of neurones in the cortex.
Describe early-stage Huntington’s disease.
Early stage Huntington’s shows an excess of movement with uncontrollable and relatively rapid motor patterns (choreiform).
The primary pathology in this stage is the loss of striatal output of the indirect pathway. This leads to an overactive thalamocortical pathway and involuntary movement.
Describe late-stage Huntington’s disease.
In the late phase of Huntington’s, there is an imbalance of DA, Ach, and GABA systems (increased DA, decreased GABA, decreased Ach).
In Huntington’s, there is an overproduction of which protein?
Huntingtin.
What genetic motif is present in all Huntington’s patients’ genes?
Individuals that develop Huntington’s have > 40 CAG repeats which encode for glutamine (not glutamate).
What do an increase in CAG repeats in Huntington’s patient’s mean?
It was found that the more CAG repeats there are, the earlier symptoms present.
How is drug therapy in Huntington’s disease limited?
Drug therapy for Huntington’s is limited to symptomatic and support therapies. Current treatments cannot reverse, stop, or even slow the progression of the disease.
What classes of drugs are used in the treatment of Huntington’s disease?
Benzodiazepines, neuroleptics, NMDA inhibitors, antioxidants, calcium channel inhibitors, NOS.
How are benzodiazepines used in the treatment of Huntington’s disease?
Benzodiazepines can be used for GABA potentiation effect at the GABA-A receptor to maximise the effect of GABA released from the remaining neurones.
What future treatments have been proposed for the treatment of Huntington’s?
It is proposed that in the future surgery of foetal striatal implants may be used to treat Huntington’s.
