Huntington's Disease
...to concentrate and learning deficits. A person with Huntington’s misses out on much of their family life and if they don’t miss out on it, it is very likely that they won’t remember the recent aspects of it. The gene responsible for Huntington’s disease is on the fourth chromosome and is known as IT15. This gene regulates, controls, or encodes the production of the protein known as huntingtin. This was a semi recent discovery seeing as it was only uncovered in 1993. This protein is found in neurons throughout the brain. Mutations of the IT15 gene result in abnormally long repeated DNA instructions. These instructions include unusual, repeated sequences of certain basic chemicals known as cytosine, adenine, and guanine. These are called CAG trinucleotide repeats. These expanded CAG sequences produce the production of the abnormal huntingtin protein. Scientists are starting to conclude that the CAG repeats might have some relation to the age at symptom onset. For example, those with a large number of repeats tend to develop symptoms at an earlier age. Extremely large CAG repeats of 80 or greater are often associated with a disease onset during childhood or adolescence. Such a correlation may be less apparent in individuals with a shorter range of CAG repeats. For CAG repeats equal to or greater than 42, the HD gene is thought to have 100 percent penetrance. One thing found that is very interesting is that the expanded CAG repeats are not stable and tend to expand from generation to generation. This is known as genetic anticipation. Evidence suggests that CAG repeats are more unstable when the diseased gene is inherited from the father. Therefore, individuals with Huntington’s disease who inherit the diseased gene through paternal transmission (from their fathers) may tend to develop symptoms at an earlier age than their fathers. While no cure yet exists, there is a large push in research to develop one and in most cases; Huntington’s patients can maintain independence for several yeas after the onset of symptoms. Treatment of Huntington's disease has been limited to symptomatic and supportive therapies. A number of medications have been introduced to treat chorea, depression, anxiety and psychosis. While some of them are quite effective for alleviating the symptoms and play essential roles in management of HD, they do not stop the disease process itself. Simply, they mask the symptoms. Supportive therapies such as nursing care, psychological adjustments, physical therapy, speech therapy, diet modifications, etc. become essential as the disease progresses. Patients with advanced Huntington’s require prevention and treatments of various medical complications. Currently available treatments cannot reverse, stop or even slow the disease process in HD. As the research started to provide increasing understanding of the disease mechanisms in recent years, there have been discussions on new therapeutic strategies. Some of them are becoming available for clinical trials, while others require further development as clinically feasible therapies. There is substantial evidence that the final pathway of cell death in the brain of HD patients involves excitotoxicity. The excitotoxic loss of neurons is mediated by binding of excitatory amino acids to their receptors. Among these excitatory amino acids, glutamate appears to produce excitotoxicity by binding to one type of glutamatergic receptor called N-methyl-D-aspartate (NMDA) receptor in HD. Drugs that inhibit the glutamatergic transmission may be useful for treating HD patients. These include blockers of a glutamate receptor, such as remacemide, and drugs that inhibit a release or synthesis of glutamate, such as riluzole (Rilutek), lamotrigine (Lamictal) and gabapentin (Neurontin). One of these medications, Riluzole, has a slight (10%) benefit on the life-spans of patients with Lou Gehrig's disease (another neurological disease known as ALS or amyotrophic lateral sclerosis, in which excitotoxicity appears to contribute to disease). Lamotrigine has failed to show efficacy in treatment of patients with HD. These current treatments of Huntington’s disease are just two of the complicated ways to relieve symptoms and suspend life for as long as possible. In order to detect Huntington’s disease, there must be very advanced ways of discovering it. Using a way we learned in class, PCR would be the method of detecting HD in the DNA. Using PCR, a scientist would take a gene from the patient and denature the double stranded DNA. Then, they would hybridize the primers (to get it started) in which lower temperatures would be required. Once the primers are hybridized, the DNA would be extended using a tag and polymerase. Once many copies are made, it would be put in gel with defective and normal DNA. T...