Huntington’s disease exists as a serious illness of the nervous system with a genetic origin and the presence of the trochaic hyperkinesis and dementia. This disease has an autosomal dominant pattern of inheritance with a high phenotypic expression of the mutant gene. The basis of the disease is gross violation of oxidative metabolism. During the diagnosis, doctors are detecting degenerative changes in the cerebral cortex and subcortical ganglia. The study of this disease began in the 19th century. Currently, doctors have discovered new characteristics and origin features. Huntington's disease is a genetic neurodegenerative brain disease caused by oxidative stress and low levels of the amino acid cysteine. It is amenable to symptomatic treatment only, and the main symptoms of the disease are the hyperkinetic syndrome and degenerative mental changes.
The History of Huntington's Disease
In 1872, George Huntington singled out an independent clinical form from the group of diseases that occur with choreatic twitching. This form was characterized by a late appearance of hyperkinesis, dementia, chronic progressive course, and genetic heredity. The reason for describing new diseases was the observations of the family members in Long Island. In fact, Huntington and his predecessors have observed different generations of this family for 75 years and localized first features of the disease. After Huntington, physicians started to describe this disease in different countries. Thus, scientists Peretti and Guber offered to name it Huntington's disease. The complete clinical response, as well as the uniqueness of the manifestations and the course of chronic progressive chorea, appeared in the later work of Huntington. Besides, the works of Muratov, Davenport and Manse, Entresa, Kehrer, Hassler, and Wilson also contained the research of this disease. In particular, they have established that the main symptoms of the disease are movement disorders and dementia that are varying both in intensity and in the sequence of their occurrence. Furthermore, scientists have determined that changes in the central nervous system have degenerative and atrophic character. Besides, they noticed that changes caused by this genetic brain disease differ from those by chorea with an infectious or arteriosclerotic origin. Thus, scientists have proven that chronic hereditary chorea has quite certain pathologic features. In spite of the considerable interest in the genetic and biochemical changes provoked by this disease, the search for disease’s genes was not successful until the late 1970s. At this time, Nancy Wexler and Allan Tobin organized a workshop sponsored by the Foundation of hereditary diseases in order to discuss the search strategy for Huntington's disease gene. David Housman, David Botstein, and Ray White suggested that the recently developed recombinant DNA techniques might help in achieving this goal. A key challenge in the prepared project was to search a large family whose members suffered from Huntington's disease in many generations. As a result, the doctors were aiming to get a DNA sample. In 1979, Venezuela and the United States launched a joint project of scientists who examined a large family with Huntington's disease. In 1983, Huntington's disease gene was localized at the end of the short arm of chromosome 4. Ten years later, scientists discovered that a mutation in this gene lies in increasing the number of trinucleotide cytosine-adenine-guanine repetitions. Therefore, the history of Huntington's disease research started in the late 19th century and achieved significant results.
The Current Information and Researcgh
Chorea Huntington is a hereditary disease of the nervous system that usually occurs between the ages of 35-45 years and is characterized by changes in cognitive and physical skills. People are living with this disease for about 15-20 years after the onset of symptoms and die, usually due to complications. However, Huntington disease has no particular preference. Modern scholars are confident that Huntingtin gene is present in all human beings without exception. This gene is located on the short arm of the fourth chromosome. Besides, a gene encodes the huntingtin protein and consists of a sequential combination of the three nitrogenous bases, cytosine, adenine, and iguanin. In this sequence, they repeated many times in different individuals. This combination of nitrogen bases called trinucleotide repeats. During this process, CAG triplet encodes glutamic amino acid. Besides, these successive chains of glutamic amino acids form the synthesized protein huntingtin. Current research has information that each person has a certain amount of repeated CAG triplets, but it must be less than 36. Their increase causes the synthesis of the elongated chain in polyglutamine tract that creates the mutated form of the huntingtin protein. This mutated protein has a negative impact on the striatum that is responsible for the coordination of movements. With the progression of the disease, mutant protein affects other parts of the brain. As a result, this mutant protein becomes the cause of the Huntington's syndrome. However, some individuals have an increased proportion of repeated CAG triplets, and this feature has a genetic heredity. Thus, external factors cannot affect the occurrence of the disease. In fact, the length of the polyglutamine tract affects the expression of the symptoms. Modern scientists have determined that the number of repeats from 36 to 40 cause a reduced penetrance form of the syndrome. This form of the disease is manifested much later and has a slow progression. If the value exceeds 605 repeats, the disease appears much earlier. With a maximum amount of repeats, the disease has an absolute penetrance and often manifests itself at an early age. This form of the disease can be called juvenile and accounts for approximately 7% of all the cases of Huntington's disease. Consequently, current research proves that this disease is inherited from parents and lies in a single gene.
Modern scientists were able to determine the mechanism of irreversible damage to nerve cells in Huntington's disease. In the new study, researchers found that nerve cell damage causes low levels of cysteine. In fact, this process became the cause of oxidative stress. Abrupt cell damage due to oxidation reduces the amount of cysteine in cells even further. The researchers discovered the cause of the lack of cysteine in the cells. They found that at low levels of amino acids healthy cells secrete cystathionine gamma-lyase by using ATF4 protein. It recognizes the DNA sequence involved in the synthesis of amino acids and gives a signal to start the production of cell protein synthesis for cysteine and other protective molecules. In cases of patients with Huntington's disease, ATF4 prohibits cells to produce cysteine, causing them to die due to oxidation. Therefore, understanding how this mechanism works will allow scientists to slow the progression of chorea in the future.
The Symptoms and Treatments
The first symptoms usually appear after 30, but there is also a low percentage of the disease occurrence at an early age. Huntington's disease is characterized by a combination of motor and neuropsychiatric disorders that can occur simultaneously or in succession. Movement disorders include involuntary grimace and excessive gestures. The patient finds it difficult to hold the protruding tongue or a clenched fist. Besides, a person cannot hold the gaze on one object. Neuropsychiatric disorders affect both cognitive and intellectual functions. Furthermore, this disease causes unstable emotional status. Emotional and behavioral disorders primarily find expression in the emergence of unmotivated aggression and irritability. Approximately one third of patients suffer from depression. Cognitive dysfunction most often expressed in problems of visual-spatial orientation, not allowing the patient to recognize the image, find objects on the screen, or the map. Huntington's disease also damages person’s memory. However, the part of the life events preservation is not violated. Because of disease, a person loses the ability to keep in mind the information necessary for the workflow, especially when dealing with multiple sources. The patients may also have difficulties in planning and organizing their activities. Over time, the severity of symptoms increases and reaches dementia. In fact, physicians perform genetic research to confirm the suspicion of Huntington's disease. The identification of the abnormal gene gives the possibility to prove the presence of the disease.
Unfortunately, modern medicine has not yet found an effective course of therapy that could overcome the symptoms of the disease. Thus, a full recovery is impossible. Physicians use only symptomatic treatment, which helps to alleviate patient's condition and slows chorea. Doctors prescribe reception of neurotrophins by which help to improve the nutrition of the brain tissue. Moreover, doctors prescribe intake of B vitamins, antipsychotics, tranquilizers, which reduce the symptoms of chorea. Physicians are using valproic acid and a variety of anti-Parkinsonian drugs to battle muscles rigidity and eliminate enhanced motor activity. Some scholars consider surgery as a way of Huntington's disease treatment. In practice, it is impossible to cure chorea in such a way. Scientists can only reduce its severity and decrease uncontrolled movements with the help of surgery for some time. However, recent studies show a positive effect of antipsychotic medications. This type of treatment is one of the most effective methods. The problem is that such drugs are banned in many countries. Furthermore, researchers are actively studying a therapy method based on the use of stem cells to stop chorea, and in some situations even to restore damaged nerve cells. However, this research has not been applied in practice. A person diagnosed with it live about 15 years, and in severe cases only eight years. If pathology begins to develop in 40 years, people do not live more than 55 years. Thus, the course of therapy prolongs life only for a few years. In order to facilitate the manifestation of the disease and prolong patient's life, doctors advise to apply early screening methods for the disease determination. Therefore, Huntington's disease is a serious and unexplored illness. Currently, scientists are actively studying its origin and general features of genetic heredity. In the future, humanity would be able to find treatment and methods of Huntington's disease prevention.
Huntington's disease is an autosomal dominant neurodegenerative disease. The main symptoms of this disease are progressive cognitive impairment and hyperkinesis that begin in middle age. Scientists named the disease after the American physician George Huntington, who first described it in 1872. Huntington's disease is a hereditary illness and an inherited genetic defect leads to a decrease in cystine level and synthesis of the pathological protein. An exposure of mutagenic protein causes the death of brain cells. Scientists confirm the diagnosis of the disease by a genetic testing. Unfortunately, this disease is incurable for modern medicine. In fact, there are special antipsychotics drugs that have a symptomatic effect and make life easier for people with the disease. Consequently, Huntington's disease is a serious genetic disorder that requires further study.