Advances in Management of Parkinson's Disease - Literature review Example

Advances in Management of Parkinson’s Disease A Review of Literature al Affiliation January 13, The first well-documented medical description of Parkinson’s disease was done in 1817 by James Parkinson hence the name (Goetz, 2011). The description was however limited and more work needed to be done to bring to the knowledge of physicians the factors leading to the disease. The mid-19th century saw great progress in the work with Martin Charcot being in the lead in refining and expounding on the early description that had been developed by Parkinson (Goetz, 2011). One of the major developments done at the time included the isolation of the disease from others depicting similar symptoms such as multiple sclerosis. Developing management plans for the disease has been a daunting task that is still being researched on. It has been established that the disease cannot be cured but it can be managed to prevent continued degeneration. Anticholinergic drugs were used at that time with the use levodopa being adopted later. This was done after the discovery of dopaminergic deficits in the pathophysiology of the disease. The disease is quite common and affects the nervous system with patients having symptoms such as tremor, slowness in movement, rigidity and instability. It’s a neurodegenerative disorder and research shows that it affects about one per cent of the population from the age of seventy (Savitt, Dawson & Ted, 2006). The greatest development in the treatment of PD was the development of ways to correct dopamine deficiency which is greatly associated with the disease. Halting disease progression has been the greatest nightmare in science and medicine as the medical therapy used is just used to provide temporary relief and not a long term solution for the disease. Keywords: Dopamine, Corpus Striatum, Bradykinesia, Degeneration, Protein Aggregation, Introduction The need, to do this research on Parkinson’s disease, was necessitated by the fact it is the second most common neurodegenerative disorder (Barbara & Lang, 2014). There are various factors associated with the onset of the disease with various genetic and environmental factors being thought to have an interaction that results to the disease (Bekris, Mata & Zabetian, 2010). Familial Parkinsonism which is detected when patients show symptoms such as rigidity, tremor and slowness in movement has been shown to be caused by mutation in six genes which include SNCA, ATP13A2, PINK1, DJ1, PRKN and LRRK2 (Bekris, Mata & Zabetian, 2010). Other factors, which have been seen as predisposing factors or leading to the disease, include variation in the MAPT, SNCA, and LRRK2. Putting the individual at a vulnerable position makes them to show the symptoms identified above and the tests done on them can identify the presence of the disease. The current treatment for Parkinson’s disease is limited with the techniques developed having various drawbacks towards its management. Therefore addressing the topic through this research and providing supplementary benefits will be of importance in trying to come up with a working strategy that can be employed in future to manage the disease’ manifestation in the body. Some of the developments that have been made and proved worthwhile in the recent past include the use of α6β2* and α4β2* nicotinic acetylcholine receptors as drug targets for the disease. This has been done specifically after realizing that though the disease fails to have a cure, researchers can bank a lot on the knowledge that drugs targeting the dopaminergic system can provide major relief by abating the symptoms (Quik & Wonnacott, 2011). Such drugs are used to improve the functional deficits depicted in persons having Parkinson’s disease. These and other developments will be evaluated in the review to develop a better understanding of the disease and the areas that can be targeted to develop a lasting solution. Parkinson’s disease and the Nicotinic Cholinergic System As indicated earlier, PD stands as the second most common neurodegenerative disorder. The most common is Alzheimer’s disease (Quik & Wonnacott, 2011). It is mainly associated with old age affecting about 1-2% of the population above the age of sixty with symptoms such as bradykinesia being evident. The symptoms seen are as a result of the acute degeneration of the nigrostriatal dopaminergic pathway which is one of the pathways in the brain and the most adversely affected in cases of PD. With genetic (familial inheritance), and the environment playing a significant part in the disease etiology, mutations to various genes indicated above in different studies as well as the PARK1 and PARK18 are responsible for about half of all the cases reported (Schapira, 2009; Schapira, Emre, Jenner & Poewe, 2009). The mutations involve point mutations and multiplications in the α-synuclein gene. This is the gene that encodes parkin. In such cases, the greatest risk or predisposition to the mutation is exposure to herbicides and pesticides. According to Lang (2009), the most effective current treatment for PD motor symptoms such as tremor and bradykinesia is dopamine replacement therapy with L-DOPA. This can also be accomplished using dopamine agonists. This technique is however marred with various drawbacks which include drug inefficiency with disease progression and serious side effects. To address those drawbacks it would be important to understand the link and the relationship between nicotinic cholinergic and dopaminergic systems. The striatum is divided into two; - the dorsal striatum which receives dopaminergic innervation and the substantia nigra pars compacta. This is the pathway that degenerates in cases of PD (Quik & Wonnacott, 2011). Alpha-Dihydroergocryptine and Premipexole Alph-dihydroergocryptine is used in symptomatic therapy to levodopa in patients having Parkinson’s disease. The efficacy target, which was used in a certain study to assess the advantages of the technique and its drawbacks, was the Unified Parkinson’s Disease Rating Scale III subscale (Ortiz, San-Juan & Scarci, 2014). The options available in the management of symptoms in PD are few. In various critical cases, surgery maybe the only feasible option. Others as will be evaluated in this section include use of dopamine agonists having been used in monotherapy and also as an adjunct therapy. However, ergot derivatives are still used and they offer a good option in the symptomatic treatment of Parkinson’s disease (Ortiz, San-Juan & Scarci, 2014). DHEC through studies done has been identified as efficacious in PD monotherapy. However, in the studies done, it was related to various adverse side effects such as nausea in majority of the patients, abdominal pain, and decreased appetite. Few cases of patient hair loss were also identified with future studies in the field being done to see what can be done to stop the side effects attributed to the use of the technique. PRAM used in this section to be compared in terms of efficacy with DHEC is also a good option and the results obtained especially with early onset patients are really good (Ortiz, San-Juan & Scarci, 2014). In the study done by Ortiz, San-Juan & Scarci, (2014), it was established that both drugs had significant effect in decreasing motor symptoms such as bradykinesia and tremor. However, it is of importance to note that there are various inter-individual variance in the way the patients respond to the drugs in terms of side effects and also in the drug efficacy. The major differences that were noted in the study that can be used to show the exact variance was that PRAM decreased UPDRS I and II in a significant manner while in the use of DHEC no notable decrease was recorded. Both drugs are however not devoid of various limitations with long term side effects being expected with continued use to treat motor symptoms. Nausea was the major short term side effect according to the study which is expected when patients are subjected to such drugs. Therefore considering the advantages and the drawbacks of the drug, we can conclude that dihydroergocryptine can be used as an alternative to premipexole in the levodopa symptomatic therapy (Ortiz, San-Juan & Scarci, 2014). Developments and Latest Research Diagnosis for Parkinson’s disease is based on the symptoms such as muscle rigidity, resting tremor, bradykinesia and postural instability (Ahlskog, 2005). It has been established however that there are other symptoms still allied to the disease such as constipation, urinary problems, and orthostatic hypotension. Other rare symptoms, which are mainly allied to the treatment used, include sexual dysfunction and excessive salivation (Johns Hopkins Medicine). As looked into in this work, the three main drugs that are used in the treatment of its symptoms-since there is no known cure-include levodopa, apomorphine and dopamine agonists. Levodopa works by replacing lost dopamine in the brain, apomorphine works with the long term cases while dopamine agonists stimulate nerve cells and often used in line with levodopa to attain better results (Stacy, & Galbreath, 2008). The three methods have been used interchangeably or interdependently to achieve the desired results. At times the side effects which are often used to evaluate whether a drug can be used are too serious. In the use of the above the known side effects include hallucinations and constant fall into deliriums. Each individual responds differently to the drugs though there is a close correlation of the side effects. The development in the industry should therefore focus on the establishment of a management plan that will have the least side effects as some of them subject the patient to more agony than the one they experience when they have the disease (Parkinson’s disease Foundation). However, many patients live well with the treatment and notable change is reported. Deep Brain Stimulation Surgery The effect of the medication described above becomes less effective with time and therefore calls for another strategy that will manage disease development. Deep Brain Stimulation Surgery has been adopted in the recent times and though not offering a cure as the previous techniques, it is good in treating the disease symptoms (Weiner, Lang & Shulman, 2006). It is employed to those who have stayed with the disease for a long period. It is a complex process that works by doing implants of leads with electrons in various parts of the brain. These include the thalamus, globus pallidus and the subthamalic nucleus (Scharz, 2012). Once installed, the device can last for about four years. Further breakthroughs are underway though at the moment it stands to be one of the best techniques in dealing with long term cases for the disease. Much work therefore needs to be done on the topic. Among the areas that need to be addressed is whether Parkinson’s disease is in any way linked to any sex chromosome since the number of men diagnosed with it are more than the women. It is also important to develop techniques that are posing less side effects unlike the ones that are already being used. The cost factor is also an important factor in PD treatment. It has been established for instance that one Deep Brain Stimulation Surgery goes for about $2000 which is beyond the ability of many people. Cheaper management is therefore needed in the field. Conclusion PD is a disease that affects the brain and the symptoms seen include tremor, bradykinesia and loss of stability while walking (Jones & Murray, 2011). It has no cure but medics have been treating the symptoms when it is established that a patient is ailing from it (Tarsy, 2014). There has been intensive research in the field with the developments done having been evaluated in the section above. New research which is underway and which may prove important in preventing and treatment include one being done by Dr. Amy Reeve from Newcastle University which is aimed at establishing and understanding the mitochondria involvement in brain death and how brain cells can be protected when they run out of energy. Another important one is being done by Dr. Monty Siverdale from the University of Manchester who is working towards establishing the cause of pain in PD. Professor Oliver Bandman from University of Sheffield is also aiming at targeting the GCase protein which can be used to slow Parkinson’s progress. On top of this it is important for the researchers to develop a way that can be used to stop the build-up of alpha-synuclein which plays a part in PD development. With such research underway it is possible to crack the code towards developing a cure for Parkinson’s disease. Bibliography Ahlskog, J. E. (2005). The Parkinson’s disease Treatment Book: Partnering with your Doctor to get the most from your Medications, 1st Ed. Oxford: Oxford University Press. Barbara, S. C. & Lang, A. E. (2014). Pharmacological Treatment of Parkinson’s disease: A Review. The Journal of the American medical Association. 311(16). Goetz, C.G. (2011). The History of Parkinson’s disease: Early Clinical Descriptions and Neurological Therapies. CSH Perspectives in Medicine. Johns Hopkins Medicine. (n.d). Neurology and Neurosurgery. Web. http://www.hopkinsmedicine.org/neurology_neurosurgery/centers_clinics/movement_disorders/conditions/parkinsons_disease.html Accessed, Jan, 2015. Jones, T. & Murray, R. (2011). Current Research in and Development of Treatments for Parkinson’s disease. The Pharmaceutical Journal. Royal Pharmaceutical Society Publication. Lang, A. E. (2009). When and How Should Treatment be started in Parkinson’s disease? Neurology, 72:S39-S43. Weiner, W. J., Lang, A. E. & Shulman, L. M. (2006). Parkinson’s disease: A Complete Guide for Patients and Families (A Johns Hopkins Press Health Book), 2nd Ed. Baltimore: Johns Hopkins University Press. Ortiz, U. R., San-Juan, D. & Scarci, F. (2014). Alpha-Dihydroergocryptine vs. Pramipexole as Adjunct Symptomatic Treatment of Idiopathic Parkinson’s. Advances in Parkinson’s disease, (4)1-8. Parkinson’s disease Foundation. (n.d). Chasing the Cure. Web. http://www.pdf.org/en/chasing_parkinsons_cure Accessed, Jan, 2015. Quik, M. & Wonnacott, S. (2011). α6β2* and α4β2* Nicotinic Acetylcholine Receptors as Drug Targets for Parkinson’s disease. Pharmacological Reviews, 63(4). Savitt, J. M., Dawson, V. L. & Dawson, T. M. (2006). Diagnosis and Treatment of Parkinson’s disease: Molecules to Medicine. American Society for Clinical Investigation. (116)7. Schapira, A. H. (2009). Neurobiology and Treatment of Parkinson’s disease. Trends Pharmacol Sci, 30: 41-47. Schapira, A. H., Emre, N., Jenner, P. & Poewe, W. (2009). Levodopa in the Treatment of Parkinson’s disease. Europe Journal of Neurology. (16). p. 982-989. Scharz, P. S. (2012). Parkinson’s Disease: 300 Tips for Making Life Easier. ReadHowYouWant Publications. Stacy, M. & Galbreath, A. (2008). Optimizing Long-Term Therapy for Parkinson’s disease: Levodopa, Dopamine Agonists, and Treatment-Associated Dykinesia. Clinical Neuropharmacology, (31), p. 51-56. Tarsy, D. (2014). Pharmacologic Treatment of Parkinson’s disease. 22(10). Read More