Huntington’s Disease Samples for Students †MyAssignmenthelp.com

Question: Discuss about the Huntingtons Disease. Answer: Huntingtons Disease Huntingtons disease (HD) is a dominantly inherited neurogenerative disorder resulting from the unstable expansion of the CAG trinucleotide in the HTT gene (Raymond, et al., 2011). The HTT gene serves as an instruction template for the protein huntingtin. The exact function of huntingtin is, however, unknown but it is proposed to play a role foetal development before birth, and also has a role in nerve cells (NIH, 2015). HD is a progressive disorder characterised by unwanted choreatic movements. Pathophysiology The expanded CAG repeat produces an extended polyglutamine tail on the huntingtin protein, and this causes the protein to cleavage and also generate toxic fragments (Jankovic Ashizawa, 2008). The polyglutamine content in the toxic fragments prompts cross-linking, and this forms aggregates that are resistant to degradation, and also causes interference with various normal cellular functions, predominantly mitochondrial energy metabolism, disrupted calcium signalling, abnormal protein interactions, transcriptional dysregulation of a variety of genes, alterations in axonal transportation of critical factors, autophagy, and altered proteasomal functioning (Zuccato, et al., 2010; Johnson Davidson, 2010). A reduction in the level of wild-type huntingtin has not shown to be contributing to the disease, it, however, magnifies the adverse effects of the generated fragments. The disease primarily affects the striatum, and the clinical presentation is primarily as a result of the damage (mainly cell loss and gliosis), include behaviour changes, cognitive impairment, and loss of coordination (Jankovic Ashizawa, 2008). Additionally, further pathological changes are also evidenced in several other cortical and sub-cortical structures (Rosas, et al., 2008). The hallmark feature of Huntingtons disease (chorea), results from striatal dysfunction. This pathological process is the most accepted and as a result, therapeutic interventions are being designed to improve mitochondrial function, facilitate retardation of apoptosis, enhance autophagic consumption of mutant proteins, block the cleavage of huntingtin at the sites that produce the toxic fragments, and also improve cell-cell interactions (Hannan, 2005). Existing treatments Drug therapy Neuroleptics such as haloperidol (typical) and olanzapine (atypical), benzodiazepines the monoamine-depleting agent tetrabenazine are used to suppress choreic movements (Huntington Study Group, 2006). While psychiatric disturbances that include depression are managed using psychotropic and antiepileptic agents (Frank, 2014) However, pharmacological treatment is only limited to the treatment of signs and symptoms and cannot change the disease development or progression (Killoran Biglan, 2014). Further, chorea may be exacerbated by L-dopa containing compounds (Warby, et al., 2014) Non-medication interventions Persons suffering from Huntingtons disease require psychotherapy from a psychotherapist to help in the management of behavioural problems, help the patient in developing coping strategies, and also manage the patients expectations through the disease progression. Speech therapy and physical therapy may also be indicated because HD can impair the control of muscles. A speech therapist will help the patient improve their ability to speak clearly, or in the use of communication devices. Physical therapy will help the patient enhance coordination, balance, flexibility, and strength. Persons with HD also require supportive care with special attention to nursing, diet, special equipment, emotional support, counselling, practical help and relief in forms such as state and federal benefits (Williams, et al., 2009). The primary inadequacy of non-pharmacological treatment is that it cannot be used as the primary treatment in the treatment of HD, but rather as secondary. Surgical treatment Surgical treatment plays a minimal role in HD. Surgical interventions are basically in the experimental phase and they include ablative surgery and cell transplantation (Demeestere Vandenberghe, 2010). These interventions show some promise but their efficacy has not been fully demonstrated. The primary advantage of surgical interventions is the possibility that they can modify the course of the disease. On the other hand, the primary disadvantage is that these procedures are that for the treatment of a widespread disease such as Huntingtons disease, the effects of the surgery tend to be confined to the local region where it is performed (Demeestere Vandenberghe, 2010). The impact on the individual health system of the disease and treatment Research on the economic cost of HD has not been well studied. There are only two notable studies on the same, one being conducted in the US (Divino, et al., 2013), and another in Europe (Busse, et al., 2011). The authors also claim that the primary cost in HD is the primary healthcare component. From the two studies, it is evident that the direct economic burden of the condition is substantial and it increases as the disease progresses. In 2013, the estimated cost for the treatment of an HD patient was $4,947 in the early HD stage, and this rises to $22,582 in the late stage, whereas in the UK, the earliest stages cost approximately 2250 per person and 89 760 in the later stages (Jones, et al., 2016). Other than the direct economic cost, HD has a significant impact on both the individual and their family. The onset of the diseases signs and symptoms is 35-45 years (Vamos, et al., 2007). This is the period when the family-life cycle is most complex, as characterised by childbearing and rearing and career development. The family suffers a great deal of distress and grief in the sense that they have to mourn those who have passed on and anticipated further losses for those who will die. Overall burden of disease It is estimated that 5 to 7 persons per 100,000 are affected by HD in the Western Countries (Australian Huntington's Disease Association, 2017). This is however not in the case as some regions of Western Europe have no HD whereas the concentration is quite high in others as evidenced in Lake Maracaibo in Venezuela where the prevalence is approximately 700 per 100,000 (Australian Huntington's Disease Association, 2017). As per the Australian Huntington's Disease Association, in Australia, approximately 1,800 people have the condition whereas another 9,000 are at risk. Its prevalence in Australia has been evidenced to increase at 15-20% per decade (Rawlins, et al., 2016). In the UK, it is estimated that 12 out of every 1000, 000 people are affected (Evans, et al., 2013), whereas in the US, 7 out of every 100,000 persons are at risk of developing the condition (Rawlins, et al., 2016). According to Rawlins et al., the lowest rates of HD are seen among Asians. References Australian Huntington's Disease Association, 2017. How Common Is Huntington's Disease (HD)?. [Online] Available at: https://www.huntingtonsnsw.org.au/information/hd-facts/how-common[Accessed 18 September 2017]. Busse, M. et al., 2011. Utilisation of Healthcare and Associated Services in Huntington's disease: a data mining study.. PLoS Curr. , 21(3), p. RRN1206. Demeestere, J. Vandenberghe, W., 2010. Experimental Surgical Therapies for Huntingtons Disease. CNS Neuroscience and Therapeutics, 17(6), pp. 705-713. Divino, V. et al., 2013. The direct medical costs of Huntington's disease by stage. A retrospective commercial and Medicaid claims data analysis.. J Med Econ., 16(8), pp. 1043-50. Evans, S. et al., 2013. Prevalence of adult Huntington's disease in the UK based on diagnoses recorded in general practice records.. J Neurol Neurosurg Psychiatry, 84(10), pp. 1156-60. Frank, S., 2014. Treatment of Huntingtons Disease. Neurotherapeutics, 11(1), pp. 153-160. Hannan, A. J., 2005. Novel therapeutic targets for Huntington's disease.. Expert Opin Ther Targets., 9(4), pp. 639-50. Huntington Study Group, 2006. Tetrabenazine as antichorea therapy in Huntington disease: a randomized controlled trial.. Neurology, 66(3), pp. 366-72. Jankovic, J. Ashizawa, T., 2008. Huntington's disease.. In: J. Noweworthy, ed. Neurological Therapeutics: Principles and Practice. London: Martin Dunitz, pp. 2550-2561. Johnson, C. D. Davidson, B. L., 2010. Huntington's disease: progress toward effective disease-modifying treatments and a cure. Human Molecular Genetics, 19(R1), p. R98R102. Jones, C. et al., 2016. The societal cost of Huntington's disease: are we underestimating the burden?. Eur J Neurol., 23(10), p. 15881590. Killoran, A. Biglan, K., 2014. Current therapeutic options for Huntington's disease: good clinical practice versus evidence-based approaches?. Mov Disord, 29(11), pp. 1404-13. NIH, 2015. HTT gene. [Online] Available at: https://ghr.nlm.nih.gov/gene/HTT [Accessed 19 September 2017]. Rawlins, M. et al., 2016. The Prevalence of Huntington's Disease.. Neuroepidemiology, 46(2), pp. 144-53. Raymond, L. A. et al., 2011. Pathophysiology of Huntingtons Disease: Time-Dependent Alterations in Synaptic and Receptor Function. Neuroscience, 15(198), pp. 252-273. Rosas, H. D. et al., 2008. Cerebral cortex and the clinical expression of Huntington's disease: complexity and heterogeneity.. Brain, 131(4), pp. 1057-1068. Vamos, M., Hambridge, J., Edwards, M. Conaghan, J., 2007. The Impact of Huntingtons Disease on Family Life. Psychosomatics, 48(5), pp. 400-405. Warby, S. C., Graham, R. K. Hayden, M. R., 2014. Huntington Disease. In: R. Pagon, M. Adam H. Ardinger, eds. Gene Reviews. Seattle: University pf Washington. Williams, J. et al., 2009. The emotional experiences of family carers in Huntington disease. J Adv Nurs, 65(4), pp. 789-98. Zuccato, C., Valenza, M. Cattaneo, E., 2010. Molecular mechanisms and potential therapeutical targets in Huntington's disease. Physiol Rev., 905(81), pp. 905-981.