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4.6. Huntington's Disease
Defining Huntington's Disease
Huntington’s disease is an inherited neurodegenerative disorder that involves progressive damage to the basal ganglia, resulting in symptoms such as dyskinesia (abnormal, involuntary movements), apparent clumsiness, lack of concentration and other cognitive problems. Although inherited, the symptoms of Huntington’s disease only become apparent in 30 – 50 year olds.
Huntington’s disease used to be called Huntington’s chorea due to the involuntary movements of the limbs and face (‘chorea’ is the Greek word for ‘dance’).
Huntington’s disease used to be called Huntington’s chorea due to the involuntary movements of the limbs and face (‘chorea’ is the Greek word for ‘dance’).
Biological Processes Underlying Huntington's Disease
In the healthy body, there is a gene in the short arm of chromosome 4 (see Figure 4.6.) that has a specific sequence of bases – CAG – that is repeated between 9 and 35 times. This gene is responsible for carrying the code that will make a protein called Huntingtin (sometimes abbreviated to HTT). The normal functions of Huntingtin are thought to include transporting materials within cells, regulation of DNA copying (transcription) and inhibition of programmed cell death (apoptosis). However, in Huntington’s disease, there are 36 or more repeats of the CAG sequence. This means that the instructions for making the Huntingtin protein are wrong, and as a result the protein is longer and becomes dysfunctional.
The faulty protein causes the death of neurons between the striatum of the basal ganglia and the cerebral cortex. Normally, the basal ganglia helps to inhibit excitatory action potentials that would stimulate excess and unwanted movements. So, when the neurons of the basal ganglia die, there is no mechanism to inhibit these messages on their way to the cerebral motor cortices. This is how abnormal and involuntary movements arise in Huntington’s disease.
A deeper dive
If you have looked at Section 4.5. Parkinson's disease, you will have heard me talk about the direct and indirect pathways. Huntington's disease is the opposite to Parkinson's disease, that is, the direct pathway dominates over the indirect pathway, meaning the motor areas of the cerebral cortex are more excitable. This is why abnormal involuntary movements are a symptom of Huntington's disease.
Researchers are not completely sure how the faulty protein causes neurons in the basal ganglia to die. However, the following mechanisms have been suggested:
The faulty protein causes the death of neurons between the striatum of the basal ganglia and the cerebral cortex. Normally, the basal ganglia helps to inhibit excitatory action potentials that would stimulate excess and unwanted movements. So, when the neurons of the basal ganglia die, there is no mechanism to inhibit these messages on their way to the cerebral motor cortices. This is how abnormal and involuntary movements arise in Huntington’s disease.
A deeper dive
If you have looked at Section 4.5. Parkinson's disease, you will have heard me talk about the direct and indirect pathways. Huntington's disease is the opposite to Parkinson's disease, that is, the direct pathway dominates over the indirect pathway, meaning the motor areas of the cerebral cortex are more excitable. This is why abnormal involuntary movements are a symptom of Huntington's disease.
Researchers are not completely sure how the faulty protein causes neurons in the basal ganglia to die. However, the following mechanisms have been suggested:
- The faulty protein stimulates an inflammatory response that begins to damage neurons.
- The faulty protein interferes with cell metabolism – this produces harmful ‘oxidative stress’ molecules.
- The faulty protein may be ‘chopped up’ in the brain and the resulting fragments induce apoptosis.
- The faulty proteins may aggregate, just like in Alzheimer’s disease, and induce apoptosis.
Diagnosing and Managing Huntington's Disease
Huntington’s disease can be diagnosed by testing for the faulty gene. Testing may be offered to those who have symptoms of the disease, and to those who have a parent with the disease. It is important to note that Huntington’s disease is classified as autosomal dominant – this means that if one parent has the disease, there is a 50% chance that a child will also develop the disease.
There is currently no cure for Huntington’s disease. Available treatments aim to help manage the symptoms.
Medications
Two types of drugs can be used for the treatment of involuntary movements. These include a group of medications called atypical antipsychotics, and a new drug called tetrabenazine. The latter is thought to work by reducing the amount of serotonin, dopamine and noradrenaline in the brain, although the exact mechanism is unknown. SSRIs, such as fluoxetine, can also be given to reduce depressive symptoms.
Speech and language therapy
Speech and language therapy can also help to improve communication and swallowing problems that occur in certain stages of the disease.
Occupational therapy
Therapists can identify practical problems that may arise in the home and provide appropriate solutions to ensure independence is maintained for as long as possible.
Diet and exercise
People diagnosed with Huntington’s disease may find it difficult to eat and maintain a healthy body weight. As such, a high calorie diet may be advised by the medical team. Exercise can also improve mental and physical health.
Other useful factsheets on living with Huntington’s disease can be found on the Huntington's Disease Association website (hda.org.uk).
There is currently no cure for Huntington’s disease. Available treatments aim to help manage the symptoms.
Medications
Two types of drugs can be used for the treatment of involuntary movements. These include a group of medications called atypical antipsychotics, and a new drug called tetrabenazine. The latter is thought to work by reducing the amount of serotonin, dopamine and noradrenaline in the brain, although the exact mechanism is unknown. SSRIs, such as fluoxetine, can also be given to reduce depressive symptoms.
Speech and language therapy
Speech and language therapy can also help to improve communication and swallowing problems that occur in certain stages of the disease.
Occupational therapy
Therapists can identify practical problems that may arise in the home and provide appropriate solutions to ensure independence is maintained for as long as possible.
Diet and exercise
People diagnosed with Huntington’s disease may find it difficult to eat and maintain a healthy body weight. As such, a high calorie diet may be advised by the medical team. Exercise can also improve mental and physical health.
Other useful factsheets on living with Huntington’s disease can be found on the Huntington's Disease Association website (hda.org.uk).
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