The Current and Potential Future Treatments for Parkinson's' Disease - Essay Example

Parkinson Disease Parkinson Disease is second most common degenerative disorder. This disease affects movement and control of an individual (Leader et al., 2006). No particular treatment and cure have been presented of the disease until now. This research paper mainly emphasizes on the current and future potential treatment of Parkinson’s disease. It shall illustrate Parkinson Disease, its symptoms, pathology, genetics, aetiology, and explores current and future treatments of the disease. Parkinson Disease Description of Disease Parkinson ’s disease is a chronic neurodegenerative disorder of the central nervous system, which is also known as idiopathic or paralysis agitans. It is the second most common neurgenerative disorder that affects about 1 million people in America and about 50,000 people in United Kingdom (Jankovic, 2007). The disease is characterized by a gradual loss of the muscular functioning and controlling, resulting in trembling limbs, stiffness and impairment balance. In other words, the disease causes the disorder of movement, motor weakness, spasticity, sensory loss, and cerebellar ataxia (Waters, 2008). It causes slowness of the movement or abnormal involuntary movement (dyskinesia) such as, tremor, chorea, mycolonus, tics and dystopian (Driver-Dunckley et al., 2003). The disease immensely affects sub cortical brain structures (basal ganglia) causing movement disorders. Parkinson’s disease results from the malfunction and the death of the nerve muscle of the brain cells called neurons. It affects neurons present in the substantia nigra. This part of brain controls the movement and coordination of the body part with the brain (Chaudhuri & Tolosa, 2009). Parkinson’s disease affects substantia nigra, eventually decrease production of dopamine in the brain causing individuals to lose control the movement normally (Olanow & Koller, 1998). Symptoms Symptoms of Parkinson’s disease are classified as Primary symptoms that are related to involuntary and voluntary motor functions usually occur on one side of the body. When the symptoms of the Parkinson appear they are mild that eventually progress with the time (Chaudhuri & Tolosa, 2009). According to the study of Waters (2008), by the time the symptoms of Parkinson’s disease appear, individuals would have already lost about 60 to 80 percent of the dopamine cells (cells that regulate and control the movement). The secondary symptoms appear when the Parkinson’s disease becomes progressive causing the loss and control of the body movement and damage of brain cell (Waters, 2008). The following is the list of the Parkinson’s disease symptoms: Primary Symptoms Tremors Tremor involves the trembling of finger, jaws, hands, feet, arms or head when the body of the individual is in rest, but it does not occur when one is involved in any task. The trembling gets worst when the individual is excited, tired or stressed Rigidity Rigidity refers to the stiffness of the limbs and trunk during movement. The rigidity may cause the muscle to become stiff that causes pain and aches, it may also cause loss of the hand movement and cramps (micrographia). Bradykinesia Bradykinesia causes difficulties to initiate the movement due to slowness of voluntary muscles. It may also affect facial muscles as a result expressionless mask-like appearance (Chaudhuri & Tolosa, 2009). Postural instability The stiffness of muscles and loss of reflexes makes it difficult for an individual to maintain a posture and maintain balance (Chaudhuri & Tolosa, 2009). Parkinsonian gait When an individual starts shuffle like walk and control on the body movement that makes it difficult for the person to walk or make turns (Chaudhuri & Tolosa, 2009). Secondary Symptoms Secondary symptoms involve neuropsychiatic disturbance that causes the cognitive disorder, speech, mood, behavior and thought disorder. The cognitive disturbance appears at initial stages that eventually increase with the duration of the time (Chaudhuri & Tolosa, 2009). It also affects memory, recalling abilities, visuospatial, anxiety, insomnia, constipation, gastric, dry eyes, urinary incontinence, orthostatic hypertension, stress etc. In addition, change in the behavior and moo alternation is also evident when the individual suffers from Parkinson disease causing cognitive impairment (Chaudhuri & Tolosa, 2009). (Witjas et al., 2002) (Factor & Weiner, 2008) Pathology Parkinson disease is a chronic disease or multicenter neurodegenerative disease that leads to the development of pathological abnormal abilities in a sequence (Chaudhuri & Tolosa, 2009). The disease affects neurons of the brain cell in a chronically, leading individual to lose control on the movement and abnormal movement (Acton, 2013). Stage 1 - According to the study of Schapira (2014) suggests that the prior effects are observed in the dorsal motor nucleus and olfactory blubs and nucleus. Furthermore, it is suggested that the loss of the olfactory can occur prior to the appearance of dopaminergic symptoms; it can be a sign to determine the risk (Driver-Dunckley et al., 2003). Stage 2 – the loss of the cell and lewy body formation occurs in the locus of coeruleus that eventually progress to the medulla and pons. Stage 3 – in this stage the cell loss and formation take place in the substantia nigra pars, leading to degeneration in the nucleus of pedunculopontine, dorsal raphe and hypothalamus. At the stage 5 and 6 affects the cerebral cortex and neurodegeneration in the regions that have already been affected (Chaudhuri & Tolosa, 2009). The staging of the Parkinson disease provides and understanding about the disease, it shall be noted that the clinical feature of the disease is diagnosed during stage 3. According to Chaudhuri & Tolosa (2009), in order to overcome prevalence of the disease, implication can be attained if the therapeutic disease is intervened or modified before stage 3 that shall prevent the progress of the disease when the dopaminergic features becomes severe (Chaudhuri & Tolosa, 2009). It is suggested that the treatment of the disease is effective on the non-dompaminergic system may prevent the non-motor complication that is characterized as the advanced stages of Parkinson Disease (Jankovic & Olosa, 2007). Progressive form of disease and their gene abnormality Disorder Locus/ Chromosome Gene Product Unverricht-Lundborg Lafora’s Disease MEERRF Sialidosis DRPLA Neuronal cerios Lipofuscinosis Infantile Late infantile Juvenlie EPM1/21q22.3 EPM2A/6q24 EPM2B/6p22.3 MTTK/mtDNA NEU1/6p21 DRPLA/12p13 CLN1/1p32 CLN2/11p15 CLN3/16p12 Cystatin B Laforin (dual-specificty phosphatase) Malin tRNA Neuaminidase 1 Atrophin Palmitoyl-protein Thioesterase 1 Tripeptidyl peptidase 1 CLN3 (membrane protein of unknown function) Aetiology Parkinson disease has been research for more than 200 years; the causes of the disease still remain unknown. In the past 10 years, the studies show that the Parkinson disease involves a combination of genetic and environmental factors (Driver-Dunckley et al., 2003). It is stated that Parkinson disease is caused by the genetic mutation that is transferred from generation to generation which results in the prevalence of Parkinson disease in families (Leader et al., 2006). Studies show that there are several genes that contribute to the Parkinson’s disease; perhaps the mutation in the LRRK2 gene is stated to have greatest contribution (Chaudhuri & Tolosa, 2009). Ageing is identified as a major factor to contribute to Parkinson disease, about 2 to 4 percent risk of Parkinson disease involves for people over the age of 20 and 2 percent in the general population (Jankovic, 2007). According to the study of Esiri and Morris (1997), there is a little evidence for inheritance factors in Parkinson’s disease and so environmental causes are thought to be potential importance (Worth, 2013). No environmental toxins have shown clear implication in the aetiology of Parkinson’s disease (Esiri & Morris, 1997). On the contrary, some of scientist suggests that Parkinson disease may cause from the environmental exposure (Driver-Dunckley et al., 2003). In addition, the epidemiological research has showed that the environmental toxins, present in the rural living, well water, manganese and pesticides (Acton, 2013). Some of the studies demonstrates that the chemical exposure has been associated with the risks of Parkinson disease (Acton, 2013). Insecticides permethrin beta-hexachlorocyclohexane , fungicide maned and the herbicides paraquat 2,4 dichlotophenoxyacetic are associated with exposure to the agent and environmental cause of the disease. However, 1-methyl-4-phenyl-1236-tetra hydropyridine (MPTP) affects on the substantia nigra producing parknsonian syndrome in the patient (Olanow & Koller, 1998). In addition, the defective metabolic functioning of mitochondira with the decrease respiratory enzyme has been associated with the Parkinson disease (Witjas et al., 2002). The production of the endogenous toxins due to the changes in the sulphure containing compound have also showed the relevance with the development Parkinson disease (Worth, 2013). Genetics According to the past studies experiences of 15 years have lead the scientist to believe that genetic majorly contributes towards the development of Parkinson disease. The research survey show that only 4 percent of the patient suffering with Parkinson’s are the result of the genetic changes that are inherited or carried for the development of Parkinson disease (Witjas et al., 2002). the study of Acton (2013) show that Parkinson is not inherited perhaps the diseases pre-exists in the population to about 15 to 25percent (Acton, 2013). The researches show that the gene mutation has showed a positive result in the development of Parkinson’s disease, affecting a very small number of families (Leader et al., 2006). These mutations immensely affect dopamine cell functioning (Factor & Weiner, 2008). it has also been observed that the gene mutation that been observed at an early age is due to the PINK1, LRRK2, DJ-1 and glucocerebrosidase (Acton, 2013). MPTP and Treatment Researches and studies have found that the MPTP (1-methyl-1-phenyl-1,2,3,6-tetrahydropyridine) is the permanent symptom that causes Parkinson’s disease that eventually destroys dopaminergic neuron, present I the substantia nigra of the brain (Leader et al., 2006). The injection of the MPPP and MPTP has showed rapid results of the Parkinson disease (Witjas et al., 2002). MPTP is the toxic substance that causes the blood brainbarrier, it kills dopamine producing neurons (Chaudhuri & Tolosa, 2009). The interference of MPP+ with the complex 1 produces an electron transport chain that affects mitochondria’s metabolism, resulting in cell death and prevents the radical development of the cells (Acton, 2013). It chain spontaneously affects the functioning of mitochondria present in the neuron, as a result depletion of dopamingergic neurons that cause severe implications on the cortical control. Barry Kidston, a chemistry graduate of Maryland United States synthesized MPPP and MPTP, and self injected its, due to which he started exhibiting symptom of Parkinson disease within three days. Through this it was evident that the MPPP and MPTP reaction and impurities are the major cause of the development of Parkinson disease (Acton, 2013). The autopsy of Barry showed that the injection of the MPPP with MPTP destructed dopaminergic neurons present in susbtantia nigra (Olanow & Koller, 1998). According to the study of Langstom (1984) conducted a research, he injected squirrel monkeys with MPTP, as a result the symptoms of Parkinson disease appeared which was further cured with the levodopa (Olanow & Koller, 1998). The study showed that the symptoms and signs of the Parkinson were undistinguished at the time the disease is stimulated, whereas the research was also conducted on the mice that showed that MPTP increased with age (Driver-Dunckley et al., 2003). These experiments and researches have lead to various experimental models that have gained the attention of scientist to study Parkinson’s physicological and physical possible treatments (Factor & Weiner, 2008). The outcome of the researches has provided a wider dimension for the scientist to study the disease in depth (Esiri & Morris, 1997). In addition, knowledge about the MPTP has allowed scientist to develop various experimental models to investigate the disease, furthermore it has provided neuron replacement surgery have been conducted through the fetal tissues implant, sub thalamic electrical stimulation and stem cell research that has showed positive impacts to understand the disease (Jankovic, 2007). The main contribution of the MPTP research leads to another animal model for Parkinson’s disease (Acton, 2013). The results of the study show that the pesticide and insecticide rotenone are the main cause of killing of the dopaminergic neuron in the rats caused by interferes of MPP+ with the complex 1 of the electron transport chain (Olanow & Koller, 1998). (Sian et al., 1999) Motor Symptoms and cell death The primary symptoms of the Parkinson disease also known as motor symptoms affects the pars compacts region of susbtantia nigra that eventually decreases the production of dopamine secreting cells (Acton, 2013). It affects five main pathways that connect the brain with the basal ganglia that is oculo-motor, motor, associative, limbic and oribitofrontal circuits (Acton, 2013). Parkinson disease affects all five pathways of the brain that eventually cause the disruption in the circuits. The main function of these circuits is to control the functioning of the movement, attention and learning (Witjas et al., 2002). the disease affects the production of the dopamine, the decline in the dopamine neuron causes affects motor system of an individual due to which the functioning and movement activities of the individual is affected. The depletion of dopamine leads to hypokinesia, leading the dysfunctioning of movement and control of individual on the body (Worth, 2013). Research and studies have showed various mechanisms for the depletion of brain cells (Olanow & Koller, 1998). One of the mechanisms illustrates that the deposit and accumulation of the protein alpha-synuclein damaged the cell, the protein present in that cells that is the michodonrial functioning leaders to the forming of inclusion that is Lewy bodies. The studies have found that Lewy bodies symptoms firstly appear in the olfactory, medulla obloganta, blub and pontine tegmentum (Olanow & Koller, 1998). The later stage of Lewy bodies lead to the development in the susbstantia nigra. The chain of protein affects neurons that eventually starts developing in the brain, midbrain and basal forebrain and finally in the neocortex (Leader et al., 2006). These parts of the brain are the main parts for the neuronal degeneration (Acton, 2013). The studies have showed that the dementia, presence of lewy bodies in the cortial areas of the brain can be the reason for the death of the cell (Olanow & Koller, 1998). The other mechanism of the death of the cells includes the dysfuntioning of proteosomal and lysosomal system (Factor & Weiner, 2008). In addition, the death of cell has been associated with the decline in the functioning of mitochondrial activities (Olanow & Koller, 1998). The accumulation of protein and iron in the cell leads to the conjunction in the protein inclusion that may lead to protein aggregation, oxidative stress and death of neuron cells (Acton, 2013). Analysis of Drug Parkinson’s disease demonstrates the symptoms of degeneration of nigrostraital pathways. There are several drugs and treatment advised for the treatment of Parkinson disease. Before deciding the treatment, it is essential to determine the condition and status of the disease. In the treatment of Parkinson’s disease one of the major drug used is the dopaminergic drug, the intake of the drug improves the motor functioning, decreases the probability of mortality and morbidity to restore normal live. Levodopa Levodopa is another most common drug to cure Parkinson’s disease. The drug allows fighting the stiffness, bradykinesia and rigidity. Levodopa has proven to be one of the most effective and prominent drugs throughout the course of Parkinson disease. The use of the drug has notified certain consequences regarding the progression and loss of dopaminergic cells. In addition, levodopa has shows motor complications such as dyskinesias. According to the study of Acton (2013), the motor complication develops at the rate of 10 percent among patients at the age of 60, whereas the development is faster among the younger onset patient that is, 70 percent that are diagnosed after three years. Scientists suggest that the efficiency of Levodopa can ne enhanced through the combination of cathechol-O-methyltransferase (COMT) inhibitor. The combination is suggested to be affective because the present of O-methyltransferase reduces the guts, increase the absorption of levodopa and prolongs the life. Dopamine Agonist The use of Dopamine Agonist is an effective drug to control the appearance of the dopaminergic symptoms. The only of agonist monotherpay or the adjunction to levadopa is an effective treatment. One of the causes of the failure of the agonist is because when the disease is at early stages the dose intake is low that abandons its results to reach an appropriate level. Agonist shall be recommended with the sufficient intake of the dose in order to control the symptoms as efficient as Levodopa. The studies show that the use of the agonist alone or with adjunction with Levodopa, monotherapy has shown similar results. In addition, the clinical benefits of agonist have showed equivalent results for a period of four years. According to the study of Schapira, the addition of a long acting ergot, non-erogots, pamipexole or repinirole, cabergoline with the agonist shall improve motor results. The use of the long agonist is an effective drug to control and manage dyskinesias. Rotigitine In the early stages of Parkinson disease, a new kind of dopamine agonist Rotigitine transdermal patch may be a useful treatment. Rotigitine patches posses’ antidepressant; it provides continuous supply of the dopaminergic effective that assess to control the effects of disease. The results of the Rotigitine are similar to like the other dopamine, such as, levodopa and apomorphine infusions. One of the side effects of the dopamine agonist is that it creates cognitive disturbance, such as, disturbance, confusion, and sleeplessness etc. Pramipexole Parkinson disease causes restless legs syndrome that causes the discomfort feeling in your legs that leads the patient to have urges to move. Another dopamine agonist of the non-erogline class, Pramipexole is used for the treatment of legs syndrome, cluster headaches, anti-depressants ad sexual dysfunction. Monoamine Oxidase (MAO) selegiline and rasagiline Monoamine Oxidase inhibitors have the potential for the disease modification of Parkinson disease. The neuroprotective effects of Monoamine Oxidase inhibitors can be an effective disease modification therapy at the early stages of the disease. It allows to treat the protein development and cluster in the mitochondria to overcome the disturbance in the neurons. The use of selegiline and rasagiline both have showed positive results to control motor symptoms of disease, with least side effects. For patients between 70-75 years with no cognitive impairment and co-morbidity are recommended to use MAO-B inhibitor to overcome the disease. Glutmaine In addition, Glutmaine is also highly recommended drug. The intake of the drug allows preserving brain tissues and prevents that damage of neurons and brain tissues. Glutathione is one of the essential chemical exist in the brain for the protection of the brain. According to William Code (2013), the use of the glutamine regulates the glutathione level in the body and fights back with the serious and severe disease such as Parkinson disease (Acton, 2013). Anticholinergic Pateints suffering from Parkinson disease leads to the emergence of variety of features classified as non-motor symptoms. The use of Anticholinergic and Levodopa in the early stages of the disease is one of widely recommended. The results of the Anticholinergic drugs are considered to have showed effective results than the dopaminergics, but it has significant side effects have been observed. It includes cognitive disturbance, urinary retention, and dry mouth. Treatment current and future Scientist and researches are still working to find improved and modified therapies to overcome Parkinson’s disease. The potential to cure the disease through the modification of the treatment method can be an effective approach (Leader et al., 2006). The disease modification therapy endures the potential benefits for the cure of Parkinson disease. Several advancement and modification in the aetiology and pathegensis of Parkinson disease with the gene mutation are identified as loci await. The risks of the environmental factors are due to the genetic exposure of susceptibility that can be eliminated with the gene mutation. The use of selegiline can reduce the probability of to use levodopa during the early 9 to 12 months of Parkinson disease. Studies show that patients that are treated with the selgiline have less deterioration as compared to the placebo patients. The neuroprotective effects of selegiline can have longer and lasting symptomatic effects. On the contrary, rasagiline is more potent MOA-B inhibitor than selegiline as it provides better symptomatic benefits. In addition, the neuroprotective effects in vitro and vivo models of Parkinson disease. It provides protection against MPTP, and it prevents damage and stabilize mitochondrial membrane to prevent the cell death. Furthermore, the Dopamine agonist is effective drug for the protection of the cells and tissues of the toxics. According to the recent study, highlights that the MPP+, 6-hydroxydopamine, rotenone, pramipexole and 3-nitropropionic acid prevents loss of the cells in the substantial nigra. The dopamine agonist provides as protective agents, without the presence of dopamine receptors. It has been determined that the CALM-PD study with the beta-CIT with the help of single photon, can be an effective cure for the disease. In addition, the recent studies show that the use of the stem cell therapy can be an effective cure for the Parkinson disease (Jankovic & Olosa, 2007). The main focus of this treatment is to protect dopaminergic neurons. The main focuses of the development of the treatment shall focus on the prevention of the non-dopaminergic features that appear in the later stage of disease. The current therapies of Parkinson disease emphasize on the symptomatic improvement of the motor symptoms of the disease that is the main cause of the loss of dopaminergic neurons (Acton, 2013). The current studies regarding the pathology and aetiology of the disease provides an opportunity for the incorporate effective drugs and treatment therapies for the disease (Factor & Weiner, 2008). This may allow determining the stages of the disease that can be identified and provided appropriate drug or treatment. In addition, the risk population provided on the genetic and clinical ground provides a potential for the protective therapies. The caveat and the interpretation of the disease allow the ideal group to identify and look carefully at the intensity of the disease. In addition, these interpretations allow the treatment of the physician and clinical treatment, furthermore it provide patients to make a judgment regarding the disease for the clinical practice. Whereas, the main focus of the physical shall remain on the consideration of the patient’s age, physician’s interpretation and co-morbidity and the information available (Esiri & Morris, 1997). Conclusion Analyzing the information it shall be concluded that the therapy options for the Parkinson disease emphasizes on the symptomatic improvements of the motor features of disease, that leads to the predominately loss of neuron in the susbtantia nigra. The main focus of the treatment shall be significantly dependent on the well acknowledgement regarding the disease and take appropriate treatment or therapy. The symptomatic treatment of disease can be effective to improve mortality and morbidity. The introduction and adjunction of different drugs can lead greater impacts in the modification of the disease. In addition, the current insight of the genetic, aetology and pathology of the Parkinson disease provides opportunities to cure the disease. Furthermore, the great insight to the risk on the population and genetic ground shall be a potential study to introduction, improvement and modification of the therapies. It is essential for the physician to carefully identify and evaluate the condition of the patient, in order to choose appropriate drug treatment. List of References Acton, A.Q., 2013. Parkinsonian Disorders—Advances in Research and Treatment: 2013. New York: ScholarlyEditions. Acton, A.Q., 2013. Parkinsons Disease: New Insights for the Healthcare Professional. Georgia: ScholarlyEditions. Chaudhuri, K.R. & Tolosa, E., 2009. Non-Motor Symptoms of Parkinsons Disease. Illustrated ed. Oxford: Oxford University Press. Driver-Dunckley, E., Samanta, J. & Stacy, M., 2003. Pathological gambling associated with dopamine agonist therapy in Parkinson’s disease. Neurology, 61(3), pp.422-23. Esiri, M.M. & Morris, J.H., 1997. The Neuropathology of Dementia. Illustrated ed. Cambridge: Cambridge University Press. Factor, S.A. & Weiner, W.J., 2008. Parkinsons Disease: Diagnosis & Clinical Management. 2nd ed. New York: Demos Medical Publishing. Jankovic, J., 2007. Parkinson’s disease: clinical features and diagnosis. Journal of Neurol Neurossurg Psychiatry, 79(4), pp.368-76. Jankovic, J. & Olosa, E., 2007. Parkinsons Disease and Movement Disorders. Illustrated ed. Philadelphia: Wolters Kluwer. Leader, G., Lucielle & Leader, 2006. Parkinsons Disease: Reducing Symptoms with Nutrition and Drugs. Illustrated ed. Cornell: Denor Press. Olanow, C.W. & Koller, W.C., 1998. An algorithm (decision tree) for the management of Parkinsons disease Treatment guidelines. Neurology, 50(3), pp.34-45. Sian, J., Youdim, M. & Riederer, P., 1999. Basic Neurochemistry: Molecular, Cellular and Medical Aspects. 6th ed. Würzburg: American Society for Neurochemistry. Waters, C.H., 2008. Diagnosis and Management of Parkinsons Disease. New York: Professional Communications. Witjas, T., Kaphan, E. & Azuley, J.P., 2002. Nonmotor fluctuations in Parkinson’s disease Frequent and disabling. Neurology, 59(3), pp.408-13. Worth, P., 2013. How to treat Parkinsons disease in 2013. 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