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Huntingtons disease is an autosomal dominant (Harper et al, 1991) neurodegenerative disorder characterized by un leading movements, cognitive loss, and psychiatric problems as described by Martin and Gusella (1986). These symptoms be connect to the death of medium spiny projection neurons in the caudate nucleus, putamen, and the cortex (Reiner et al, 1988). In later st get on withs of the disease, heretofore areas such as the hippocampus and hypothalamus gets stirred as well (Kassubek et al, 2004). Huntingtons disease has a prevalence reckon of approximately 1 in 10,000 Caucasian populations (Harper et al, 1991).Patients with Huntingtons disease most typic wholey display a choreic movement disorder involving involuntary wriggling movements observed by George Huntington himself. The age of onset of Huntingtons disease shake off the appearance _or_ semblance to be publicly distri buted around the average age of 35 to 42, with base number of cases developing in patients youn ger than 20 days of age or older than 60 years of age (Andrew et al, 1993). The majority of insipid patients, whose disease onset are at age 20 years or less, have inherited the paternally defected gene (Andrew et al, 1993).Patients usually died indoors 15 to 20 years of disease onset. Gusella et al (1983) first set the location of the contagious transformation in Huntingtons disease to be the short arm of chromosome 4. It was after anformer(a) 10 years did the researchers of The Huntingtons Disease collaborative Research Group (1993) up to(p) to discover that a gene in chromosome 4 containing a trinucleotide recapitulate of CAG was abnormally expand in diseased individuals. The IT15 (interesting transcript 15) gene, dubbed the huntingtin gene by the group, codes for the huntingtin gene.This CAG paraphrase, which translates into a poly-glutamine stretch, is super polymorphic among the population ranging from 11 to 34 copies on normal individuals. However, in individuals wit h Huntingtons disease it expanded to to a greater extent than 42 reverberates and increasing to upwardly of 100 (The Huntingtons Disease Collaborative Research Group, 1993). This provides evidence masking that the sport huntingtin protein seems to be toxic to its native cells and confers a disease put forward to individuals with an extended length of repeats. There is in addition a correlation between the CAG length and disease onset as shown by Andrew et al (1993).The mutated prolonged huntingtin protein is cut by enzymes into fragments and the fragments begin to form abnormal clusters, nervous intranuclear inclusions (NIIs), inside cells. These clusters hindquarters also act to recruit normal proteins to adhere in concert as well (Davies et al, 1997). This was originally thought to cause the pathogenesis of Huntingtons disease. However, much recent studies have shown that the presence of NIIs is actually a coping chemical reaction to the toxicity of mutant huntingtin pr oteins and acts to prolong the life of the cells and reduce intracellular mutant huntingtin in neighbouring neurons (Arrasate et al, 2004).The exact function of the wild-type huntingtin protein are unclear, however m whatever efforts have been made in understanding its native functions. Nasir et al (1995) showed that homozygous huntingtin homologs in mice died before embryogenesis could occur and that heterozygotes displayed similar deficits as diseased human patients. Wild-type huntingtin is also crucial for establishing and maintaining neuronal identity, especially in cortex and striatum (Reiner et al, 2001).Current info lowlife provide the conclusion that normal huntingtin protein has actions important for development in mammals. In vitro, wild-type huntingtin have been shown to act to protect brain cells from apoptotic stimuli, such as serum deprivation, mitochondrial toxins, or the transfection of death genes (Cattaneo et al, 2005). Wild-type huntingtin protein, non mutated , stimulates brain-derived neurotrophic factor (BDNF) production by acting at level of Bdnf transcription. BDNF is very important for survival of striatal neurons (Cattaneo et al, 2005).Intracellularly, huntingtin protein has been form to associate with various organelles such as the nucleus, endoplasmic reticulum, and Golgi complex (Cattaneo et al, 2005). It has also been instal in neurites and at synapses, where it associates with vesicular structures and microtubules (Li et al, 2003). This characteristic has been shown to enhance vesicular assault of BDNF along microtubules (Gauthier et al, 2004). On a similar note, huntingtin interacts with a number of cytoskeletal and synaptic vesicle proteins that are essential for exo- and endocytosis at synaptic terminals.Wild-type huntingtin binds directly to the Src homology 3 domain of postsynaptic density protein 95, which binds NMDA and kainite receptors. This activity is decreased in mutant proteins and butt joint lead to overactiv ation or sensitization of NMDA receptors (Cattaneo et al, 2005). Aside from the toxicity of the mutated huntingtin protein, the loss of normal huntingtin protein also seems to add to the pathogenesis of Huntingtons disease. Presence of tho mutant huntingtin protein results in massive apoptotic cell death in the testes of male mice (Leavitt, 2001).However, no programmed cell death bear be seen in testes of mice expressing human mutant huntingtin when wild-type huntingtin is expressed as well (Leavitt, 2001). It was also seen that in mice, the absence of wild-type huntingtin protein led to a fall of striatal atrophy and neuronal loss, and a significant decrease in neuronal cross-sectional area compared to mice that had wild-type huntingtin present (Cattaneo et al, 2005). Huntingtons disease tranquillize the Great Compromiser incurable to this day. However, m both treatments are available for treatments of its symptoms.Chorea, the hallmark of the disease is a major target for mever y treatments. Such drugs include dopamine-depleting agents, dopamine antagonists, benzodiazepines, glutamate antagonists, acetylcholinesterase inhibitors, dopamine agonists, antiseizure medications, cannabinoids, lithium, deep brain stimulation and fetal cell transplantation (Frank and Jankovic, 2010). matchless notable drug currently in use is Tetrabenazine, which is the only US FDA-approved drug for treatment of Huntingtons disease (Frank and Jankovic, 2010).The drug acts by reversibly inhibiting the central vesicular monoamine transporter type 2, this cause a depletion of dopamine (Bagchi, 1983). The main area of depression for tetrabenazine is in the caudate nucleus, putamen, and the nucleus accumbens, all areas known to be responsible for the major pathology of the disease. The Huntington Study Group (2006) was able to demonstrate the efficacy of tetrabenazine in a double-blind, placebo-controlled trial. Subjects who received tetrabenazine showed a transmute from the baselin e in the maximal chorea score of the UHDRS.Compared to the baseline, treatment resulted in a reduction of 5. 0 units in chorea compared with a 1. 5 unit reduction for the placebo group. A second symptom targeted for treatment to countenance patients to function normally is the psychiatric problems. Dopamine receptor blocking agents are commonly used as anti-psychotics in order to treat psychosis associated with Huntingtons disease (Frank and Jankovic, 2010). There are many ethical show ups that have been associated with Huntingtons disease patients, in particular pertaining to the application of communicable examination.The expanded CAG repeats associated with Huntingtons disease (Gusella et al, 1983) are used as a prophetic examination to determine the endangerment of a person for developing inherited HD gene. The give of ethics with respect to patrimonial testing for Huntingtons disease seems to double-dealing on several major factors including autonomy, beneficence, confi dentiality, and justice (Huggins et al, 1990). The question remains whether or not the current use of genetic predictive testing is ethical. familiarity refers to the respect for the individuals right to make an informed ending about an action that whitethorn have a profound effect on his or her life.The patients should feel no pressure from doctors or institutions with regards to their finale for genetic testing. Also, they should also have a full understanding of the consequences and implications of their decisions. This would shoot physicians to provide all the necessary information to the patients so that they are informed about the testing. If a woman refuses to get tests done for her botch veritable(a) though her relatives are with her insisting on getting it performed, the physician cannot bear the testing to be performed.Beneficience is summarized by the phrase first do no equipment casualty (Huggins et al, 1990). This is an important factor when the results of th e test may reveal genetic information about oneself. This implies not only avoiding harm to patient but also preventing harm to otherwise individuals, which may include family members of patients. Due to the genetic characteristics of Huntingtons disease, family members can be both directly and indirection influenced by the results of the test.If for physical exercise a pregnant woman decides to get an ultra sound for her baby in order to find out if the baby has spina bifida, and upon confirmation by the physician decides that she wants to give birth at home as irrelevant to in a hospital where the baby could be treated properly in order to minimize the luck of the disease. The physician should take any action he can in order to avoid any risk to the health of the baby. Confidentiality with genetic tests applies the same as with any other form of personal information. It should not be disclosed to any other third parties, which includes family members as well.For example, if t wo siblings were to go and receive a CAG repeat test at the same time and one sibling asks the physician about the results of the other sibling. The physician cannot disclose any information or they will violate the confidentiality of the patient. Justice simply means equal nettle to health services and information to all. This also includes long-term support and guidelines for testing as a medical service so that the service is not difficult to obtain if needed. For example, even though Cystic Fibrosis is mostly only prominent in Caucasians, the testing should still be offered to regnant women of other ethnicities as well. Other ethical quandarys still exist with current genetic testing technologies. One particularly pertaining to Huntingtons disease is whether or not the information is obtained even though there is no cure for the disease. In diseases such as phenylketonuria (PKU), after newborn screening, dietary interventions will allow the individuals with the condition to lea d healthy and normal lives (Lea et al, 2005). However, for Huntingtons disease, even after knowing that the disease will affect the individual what can be done?Therefore, would it be better to not know at all? By testing and finding out that an individual has the mutation that will eventually lead to the development of Huntingtons disease, the individual can attend to the initial development of symptoms and as a result may be treated much earlier. This can result in a more favourable prognosis. Similarly, the individual can live more guardedly as to prevent further exacerbation of their condition. On a more subjective level, the individual may use the knowledge to live a more fulfilling life knowing that he or she may not live as long as the rest of the population.Conversely, the information can also be used negatively. There can be a lot of discrimination in terms of applying for employment and health insurance. This information would also impact the ambition and life goals of the individual, the amount of psychological harm that comes with eventually developing an incurable and lethal neurodegenerative disease is extremely large. Similarly, would they still pursue to have a family and children if they knew that they had a very high risk of dying at a young age? This particular issue should be resolved by following the ethical factors listed before.As long as the individual is informed, are being prevented from harm, information not shared with any third party members, and has access to healthcare services, then being time-tested for Huntingtons disease will be ethically correct. This knowledge will give them insight on how to live the rest of their life. Another dilemma that has Harper, P. S. , Morris, M. J. , Quarrell, O. , Shaw, D. J. , Tyler, A. , and Youngman, S. (1991). The epidemiology of Huntingtons disease. J. Med. Genet. 89 365-376. Martin, J. B. , and Gusella, J. K. 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(1997).Formation of neuronal intranuclear inclusions underlies the neurological disfunction in mice transgenic for the HD mutation. Cell. 90 537-548. Arrasate, M. , Mitra, S. , Schweitzer, E. S. , Segal, M. R. , and Finkbeiner, S. (2004). Inclusion body forma tion reduces levels of mutant huntingtin and the risk of neuronal death. Nature. 431 805-810. Frank, S. , and Jankovic, J. (2010). Advances in the pharmacological management of Huntingtons disease. Drugs. 70 561-571. Bagchi, S. P. (1983). Differential interactions of phencyclidine with tetrabenazine and reserpine affecting intraneuronal dopamine.Biochem Pharmacol. 32 2851-6 Huntington Study Group. (2006). Tetrabenazine as antichorea therapy in Huntington disease a randomized controlled trial. Neurology. 66 366-72 Huggins, M. , Bloch, M. , Kanani, S. , Quarrell, O. W. , Theilman, J. , Hedrick, A. , Dickens, B. , Lynch, A. , and Hayden, M. (1990). 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