Recent Advances in the Treatment of Parkinsons Disease - Essay Example

Recent Advances and the Future Direction for Treatment of Parkinson's disease Introduction: Parkinson’s disease (PD) is the most frequently seen neurodegenerative disease after Alzheimer’s disease, which afflicts one in every hundred individuals above the age of sixty-five. The characteristic feature of PD is the loss of dopaminergic neurons within the substantia nigra pars compacta, along with the depletion of striatal dopamine. This affliction of the central nervous system results in severe difficulties with body motion that are demonstrated through tremors, rigidity, slowed body movements, unstable posture and a shuffling gait. Despite all the advances in medical science and technology, no cure has been found for the disease, with the range of pharmacological and non-pharmacological treatments providing only symptomatic relief to those afflicted with PD. (1). Recent Advances in the Treatment of Parkinson’s disease: According to Lang and Obeso, 2004, the introduction of levodopa was the first revolutionary treatment advancement for PD and the subsequent advances in pharmacological and non-pharmacologically advances in the treatment of PD have hardly offered anything substantial over the best response seen with levodopa. (2). Pharmacological Treatment Advances: The pharmacological treatment interventions for PD have essentially been levodopa as the key component, along with DA receptor agonists, selegiline, amantadine, catechol-o-methyl transferase (COMT) inhibitors and anticholinergics. Given that none of these treatments have been able to offer any cure probabilities or really prevent the progress of the consequences of the disease, it is not surprising that a lot of research has gone into finding better means to treat PD. The result of such efforts have led to the development of new neuroprotective agents like nicotine, anti-inflammatory agents, melatonin, monoamine oxidase-B (MAO-B) inhibitors, selenium, iron-chelators, Vitamin A, C & E. (1). Nicotine stimulates the release of dopamine from the striatum and through this action offers protection to the nigrostatial neurons from degeneration in PD. Inflammation is believed to be a factor in the development of PD. Studies that have examined the role of anti-inflammatory agents in providing neuroprotection, have found that the non-selective COX-inhibitor aspirin and the COX -2 preferential inhibitor meloxicam offer neuroprotection and hence the rationale for their use. Melatonin is a hormone that is naturally produced in the body, whose concentration in the body reduces in the aging process. Melatonin has anti-oxidant properties, due to its action as a free radical scavenger and demonstrates the capability of causing reduction in the production of dopaminergic neurodegenerating hydroxyl free radicals. Novel MAO-B inhibitors like rasagiline, show effectiveness in alleviating the symptoms of PD and reducing the progression of PD. Selenium is a trace element that is essential for proper body functioning, as it a vital component of many of the enzymes found produced in the human body. The essential benefit derived in PD with treatment using selenium results from its role in the functioning of the antioxidant enzyme glutathione peroxidase, which is responsible for the prevention of dopaminergic degeneration in the substantia nigra. The protein a-synuclein is a significant component of cells in the central nervous system. There are indications that the aggregation of this protein into fibrils has a part to play in the development and progress of PD in an individual. Evidence from studies show that iron hastens the abnormal aggregation of a-synuclein in PD, from which has emerged the rationale for the use of iron-chelators like desferoxamine in PD to reduce the abnormal aggregation of a-synuclein. Increased levels of lipid peroxidation are seen in the substantia nigra of patients with PD, which suggests that the presence of excess levels of free radicals have a role to play in the neurodegeneration of the nigra striatal. Vitamins A, C and E are well known antioxidants that have the capability to prevent lipid peroxidation through their free radical scavenger function. This neuroprotective function acts as the new basis for the treatment of PD, using vitamins A, C and E. (1). Surgical Treatment Advances: The use of surgical procedures to alleviate the symptoms of PD and hinder the progress of the disease is not a new concept. However, better understanding of the pathophysiology of PD has enabled new surgical approaches, which has led to ablative techniques that include pallidotomy, thalatomy and subthalatomy. (3). Studies comparing the use of these surgical intervention procedures with the best pharmacological approaches suggest that the results obtained with these surgical intervention procedures were as good or of not better than the best pharmacological approaches. The symptoms of PD that through these surgical interventions showed improvement, included contralateral tremor, rigidity, bradykinesia, gait, ipsilateral, dyskinesia and drug induced dyskinesia. Side effects remain an area of concern. However, to avoid complications seen with the surgical processes certain precautionary steps of appropriate screening and selection of patients and precise targeting are essential. (3). The concern for the side effects seen with the ablative procedures has given rise to deep brain stimulation (DBS), which has been successfully used in the internal globus pallidus, subthalamic nucleus and thalamus in the treatment of PD. DBS offers distinct advantages over the surgical ablative procedures. These advantages include the non-destructive and reversible nature of DBS, lowering the possible risks of the production of neurological deficits; stimulation parameters may be so set as to minimize any possible side effects and non-exclusion of patients from any future neurorestorative treatments that may be developed in the future. The benefits derived through DBS in the treatment of PD include improved motor function, improvement in activities of daily living, tremor suppression, reduction in rigidity, improvement in bradykinesia and reduction in painful dystonias. (4). Future Directions in the Treatment of Parkinson’s disease: Trials are already on for a vaccine that has been developed for PD. Trials in animals have been successful and human trials of the vaccine have started and if successful will pave the way of preventing PD is individuals found to be susceptible to PD. This vaccine stimulates the immune system to act against the abnormal form of protein a-synoclein, which is responsible for the pathway to neurodgeneration. (1). Transplantation of dopamine-producing neurons as replacements for those that have degenerated in the development of PD is a new direction in the treatment of PD that offers the means to allow full restoration of the functional capacity of individuals with PD. Trials have shown that there is minimal rejection of these grafts and even permit the withdrawal of levodopa therapy in PD. (1). An offshoot of the transplantation of dopamine-producing neurons is the possibility of developing gene therapy procedures. The gene therapy procedure will involve the use of several potential genes that show the capacity to increase the production of dopamine and involve a variety of gene delivery means. (5). Transplantation of foetal/embryonic brain tissue as a possible treatment for PD brings into relevance the use of stem cell therapy for the treatment of PD, with the use of stem cells as the starting donor material. For the purpose of using stem cells in the treatment of PD all three categories of stem cells namely neural stem cells, embryonic stem cells and other tissue-specific stem cells, like bone marrow stem cells may be found useful with each offering distinct advantages and disadvantages. (6). Stem cells do hold out hope as a new treatment for Parkinson’s disease, but before it really becomes a reality the several hurdles and challenges that it faces needs to be overcome. These hurdles include determination of the adverse event profile associated in its use in PD, efficiency in addressing both the dopaminergic and non-dopaminergic symptoms of PD and addressing societal and ethical issues involved in any stem cell therapy. (7). Literary References 1. Singh N, Pillai V, Choonara YE. Advances in the treatment of Parkinson’s disease. Progress in Neurobiology 2007; 81: 29-44. 2. Lang EA, Obeso AJ. Challenges in Parkinson’s disease: restoration of the nigrostatial dopamine system is not enough. THE LANCET Neurology 2004; 3: 309-316. 3. Walter BL, Vitek JL. Surgical treatment for Parkinson’s disease. THE LANCET Neurology 2004; 3: 719-728. 4. Bittar GR. Neuromodulation for movement disorders. Journal of Clinical Neuroscience 2006; 13: 315-318. 5. Allain H, Bentue-Ferrer D, Akwa Y. Disease modifying drugs and Parkinson’s disease. Progress in Neurobiology 2008; 84: 25-39. 6. Morizane A, Li J, Brundin P. From bench to bed: the potential of stem cells for the treatment of Parkinson’s disease. Cell Tissue Research 2008; 331: 323-336. 7. Snyder BJ, Olanow CW. Stem cell treatment for Parkinson's disease: an update for 2005. Current opinion in neurology 2005; 18(4): 376-385. Read More