Huntington's disease, often called Huntington's chorea, is a progressive degenerative disease which ultimately results in the death of brain cells. The video below shows a patient symptomatic of chorea, a condition of Huntington's in which manifests itself through the lack of control over one's movements. resulting in what looks like a series of twitches and jitters.
The word 'chorea' comes from the Greek choreography, meaning 'to dance'. But trust me, nobody is dancing and excited over this horrible disease. The symptoms of Huntington's amplify in their intensity the longer the patient suffers from the disease. Almost 90% of patients develop these symptoms, which often indicate that a patient may be close to death.
Over time, Huntington's disease impairs an individual’s ability to reason clearly, to walk and to speak. It destroys their quality of life, and eventually, the disease's victims succumb to death.
Huntington's disease is considered to be an "autosomal dominant" disorder, meaning that someone only needs to inherit a single copy from either parent in order for that individual to actual have the disease.
Consequently, offspring of a parent will always have a 50% chance at actually being positive for Huntington's. Because of this high rate of inheritance for prospective offspring (coupled with the fact that the contraction of Huntington's is not increased by environmental factors), Huntington's is mainly monitored if it is known that the disease runs in the family.
From a biological standpoint, the 'culprit' behind Huntington's disease is a CAG trinucleotide repeat. In a normally individual, there is caused by an increase in the size of the CAG segment leads to the production of an abnormally long version of the huntingtin protein. The elongated protein is cut into smaller, toxic fragments that bind together and accumulate in neurons, disrupting their normal functions. The dysfunction and eventual death of neurons in certain areas of the brain underlie the signs and symptoms of Huntington disease.
The Huntingtin gene provides the genetic information for a protein that is also called "huntingtin". The genetic code for this protein is found on chromosome 4. In a normal individual, the number of CAG repeats in a specific section on this chromosome are between 10 and 35 repeats, which is considered 'healthy'. For an individual with Huntington's, the number of CAG codons is anywhere above 36, but can be as high as 120 repeats in some rare cases.
Expansion of CAG (cytosine-adenine-guanine) triplet repeats in the gene coding for the Huntingtin protein results in an abnormal protein, which gradually damages cells in the brain. As of right now, we do not fully understand the way in which Huntington's manifests itself at the microscopic level.
Huntington's disease affects the HTT gene, which codes for the protein huntingtin. If an altered HTT gene is passed from one generation to the next, the offspring will always show the disease (It does not go away for a generation like many other diseases). Additionally, the size of the CAG trinucleotide repeat can increase in size from generation-to-generation, making individuals with a higher number of CAG repeats at an increased risk of having Huntington's become prevalent in either their offspring or in a future generation. Also, a larger number of repeats is usually associated with an earlier onset of signs and symptoms.
People with the adult-onset form of Huntington disease typically have 40 to 50 CAG repeats in the HTT gene, while people with the juvenile form of the disorder tend to have more than 60 CAG repeats. The juvenile form, while less common than the adult-onset form, often leads to quicker death, progressing more quickly.
More than 40 repeats of this CAG codon will always result in the development of Huntington's. Anywhere between 36 and 40 repeats usually means that an individual will develop Huntington's sometime in their life. These people are considered to be at "high-risk" for either developing the disease later in life and if they do not, likely passing on Huntington's to their offspring.
Huntington's disease manifests itself, visibly, through changes in the brain. CT scans and MRI scans can show distinct brain area shrinkage associated with certain regions of the brain (caudeate nuclei, which is a part of the basal ganglia, and the 'putamen') while other areas, like the ventricles, are often enlarged. Usually, these brain scans are only reserved (due to the fact that Huntington's only usually occurs between 3 and 7 times per 100,000 people) for those who have a known history of Huntington's in their bloodline.
The utilization of state-of-the-art techniques, in combination with a review of an individual's family history and overview of symptoms allows for an accurate diagnosis to made for the disease. Interestingly enough, many individuals who have a family history of the disease do not want to know if they have the disease or not.
What is being done in research facilities to find a possible cure for Huntington's?
While there isn't as extensive funding for the research of Huntington's compared to the funding for potential cures of various cancers and other 'more public' conditions and ailments. The research being done right now is mainly correlation-based.
Huntington's cytosine, adenine and guanine codon code for the amino acid 'glutamine'. As of now, Huntington's is one of 14 'polyglutamine diseases'. Stanford University has developed 'Huntington's Outreach Project For Education' to learn more about the disease itself. The project is currently looking at similarities between Huntington's and the 13 other polyglutamine diseases, hoping to acquire further information that could serve as a possible lead. Other brain studies also are attempting to compare fMRI and CT scans with other new research in hopes of finding a possible cure, which, as of now, there is none.
A portion of the most recent research in finding a cure for Huntington's disease is focused around some specific underlying brain parts.
One of the underlying brain parts which is currently being looked into for a possible cure is the Basal ganglia, comprised of nuclei located at the base of the brain.
The Basal ganglia acts like a conductor by orchestrating incoming signals from various parts of the brain. Holistically, it functions in the complex interactions of inhibition/excitation responses of neurons.
The brain structure plays a role in the regulation of motor control. Dopamine, a neurotransmitter which is associated with Parkinson's, is associated with this area of the brain at the synaptic level. Huntington's chorea is very similar to Parkinson's, and involves the loss of this exact motor control. Leading research suggests that an answer might not be available to the scientific community until more is understood about the neural toxic biproducts, which are somehow correlated to the extra CAG repeats.
What does the future hold?
In the future, Huntington's is likely going to become more and more prevalent. The CAG trinucleotide repeats which are the underlying factors for Huntington's are likely going to become more prevalent. There are 30,000 Americans who currently suffer from the disease, but estimates predict 200,000 people are currently at risk for it.
Funding may be limited in comparison to other major diseases in America, but it's a disease that simply shouldn't be ignored due because the nature of the disease suggests that it will only become more prevalent due to sheer number of individuals that are considered to be at risk for the disease.