IndexSymptomsIncidence/EpidemiologyCauses of Huntington's diseaseDiagnosisAvailable treatmentConclusionHuntington's disease (HD) is a rare autosomal dominant inherited progressive neurological disorder characterized by damage to neuronal cells. Although the genes responsible for HD can be found in every individual, only extensive HD will cause the disease. HD occurs due to the presence of the HTT gene mutation that generates the expansion of the CAG trinucleotide repeat. A healthy individual will have 10 to 35 CAG repeats, while HD patients typically comprise 40 or more CAG repeats. This leads to excessive production of Huntingtin proteins that alter the formation of functional proteins, thus inducing the accumulation of toxic fragments that progressively damage neurons. Because Huntington's disease is an autosomal dominant inherited disease, the offspring of the affected individual will have a 50% chance of inheriting the disease even when only one of the parental genes is affected. It is known that the course of this disease lasts from 15 to 20 years. Infections, injuries and heart failure are the most common causes of death for patients with Huntington's disease. Say no to plagiarism. Get a tailor-made essay on "Why Violent Video Games Shouldn't Be Banned"? Get an original essay Symptoms Huntington's disease is characterized by involuntary movements, memory loss, and impaired cognitive, speech, and coordination skills. There are 2 main types of HD which are distinguished based on the age of onset. The early-onset form is also known as juvenile Huntington's disease, whose symptoms begin to appear during childhood or adolescence. Juvenile HD is commonly characterized by the onset of disease symptoms at age 20 or younger. This constitutes almost 7% of cases. Early signs of juvenile HD are associated with poor learning performance, seizures, and problems with acting including, but not limited to, erratic walking and slow speaking. Aside from the juvenile case which is rare, adult onset is more common as most HD symptoms begin to appear at the age of individuals 30 years and older. Basically, HD initially presents with mild symptoms, such as difficulty concentrating, behavior, mood effects, or clumsiness. As time passes, problems with memory loss, limb coordination, the ability to think, depression, or even normal living skills such as swallowing and breathing will become increasingly worse due to reduced brain function in the control muscle movements. Incidence/Epidemiology In general, both men and women have an equal chance of inheriting Huntington's disease from their ancestors. However, in terms of disease severity, an ANCOVA analysis of motor and functional assessment of Huntington's disease patients aged 20 to 60 years showed that the rate of disease progression is slightly higher in women than in men. men. Huntington's disease is more likely to affect descendants of Europe, North America, and Australia than Asian descendants, with an overall prevalence of 5.70 per 100,000 for the former and an overall prevalence of 0.40 per 100,000 for the seconds. This result is supported by Rawlins et al. and Baig et al. in 2016. Causes of Huntington's Disease In 1872, George Huntington was the first person to provide a complete description of adult-onset HD. [HeidiIn,2008]. The HD gene, Htt, was mapped by James F. Gusella on a human chromosome in 1983 [Gusella et al.,1983]. The Htt gene was found onchromosome 4 (4p16.3) that influences the production of neurons throughout the brain, while the specific role of Htt is unclear. Unlike normal individuals, HD patients are made up of multiple trinucleotide repeats that are thought to cause toxicity to brain cells, particularly the basal ganglia and parts of the cortex. This could be demonstrated by the fact that affected movement control and thinking ability are mainly coordinated through the basal ganglia and cortex. The protein aggregation caused by the Htt gene was due to excess glutamine residues translated from the CAG repeat and caused the abnormal folding of mHtt which consequently forms more protein aggregates. One of the hallmarks of HD was the presence of dead neurons that were located primarily in the striatum. One of the most significant potential pathways for HD pathogenesis is transglutaminase. Transglutaminase causes neuronal aggregation. The discovery of the transglutaminase pathway leads to the introduction of cysteamine which inhibits the pathway. Diagnosis Nowadays, the most common and accurate form of diagnosis for Huntington's disease is genetic screening of the blood sample. People who contain 36 to 39 copies of CAG repeats in the HTT gene are considered high risk as this group of people may or may not develop symptoms. On the other hand, a person who contains more than 40 copies of the CAG repeats will develop the disease since they contain a fully penetrant gene. Since Huntington's disease is an inherited neurological disorder, neurologists will also investigate the individual's pedigree, perform linkage tests, and examine the individual's physical function before leading to a final diagnosis. Treatment available today, the pathophysiological pathways of mutated HD leading to cognitive and psychiatric changes are still unclear. This is why the search for a disease-modifying treatment is very challenging. Therefore, there is still viable disease-modifying therapy available for HD. Currently, medications prescribed to HD patients only help relieve the non-motor symptoms caused by HD. For example, tetrabenazine (TBZ) is the only FDA-approved HD drug that relieves the symptoms of chorea. While other medications such as dopamine antagonists are commonly suggested as a treatment for chorea, none of the medications have been shown to be effective in randomized, double-blind, or placebo-controlled trials for reducing chorea symptoms. This has highlighted the importance of discovering a more effective treatment for this progressive and complex disorder which is known to cause a range of non-motor problems. All experimental research aiming to identify a potential therapy for HD mainly focuses on targeting mHtt which has proven to be the responding gene. This is important for understanding the signaling pathway that leads to cell death and the pathways that reduce and inhibit mHtt. During the late 1990s, Melino et al. 1998 and Lesort et al., 2000 highlighted the potential of transglutaminase inhibitors such as cysteamine promoting neuroprotective effect as a disease-modifying treatment for neurological diseases. This statement is strengthened by the Institut Curie which demonstrated the power of cysteamine in the specific treatment of Huntington's disease. Cysteamine is a reduced form of cysteamine that can be found in mammalian cells as a product of coenzyme A metabolism. The blood-brain barrier-crossing nature of cysteamine makes it a highly promising candidate for HD therapeutic applications. The effect of cysteamine on HD was initially.