Neurodegenerative Diseases: Systems, Causes and Treatments

Neurode factorrative Diseases Sy arcs, Causes and TreatmentsSimon MendyComp be the symptoms, causes and available or future regalements for go neuron Disease, spinal anaesthesia Muscular Atrophy and myasthenia gravis Gravis.Neurodebrokerrative hazardions are inheritable (inherited) and sporadic (acquired during a individuals sustenance) conditions ca utilize by progressive anxious(p) establishment dys mesh (http//ec.europa.eu/wellness/major_chronic_ illnesss/ maladys/brain_neurological/index_en.htm). Motor neuron disease and Spinal Muscular Atrophy (shrink) are neurodegenerative conditions that arise imputable to labor neurons dysfunction and Myasthenia Gravis is an autoresistant neurodegenerative disorder. Motor neuron disease is ca utilise by defile to beat back neurons Spinal whole shrink is repayable to deterioration of the aim neurons connecting the brain and spinal stack Myasthenia gravis is an autoimmune condition that arises due to the dam fester or blocki ng of muscle receptors by antibodies accidently produced by the immune sy base of operations. All three disorders result in weakness, making there diagnosing very hard, because weakness is a very common symptom of legion(predicate) conditions. However, possibilities are ruled out depending on the age of the soul affected. If mortal exhibiting muscle weakness is 1 year old, it is to a greater extent likely that the person has SMA than the MG or MND, because SMA mainly affects children ranging from less than six months to around the age of three, whereas MND is common in teenagers and young adults, and MG normally affects middle sr. adults.Motor neurone disease is a unique condition of unknow etiology that occurs when tug neurons (specialist nerve booths in the brain and spinal stack that pass signals from the brain to the muscles) become wrongd and ultimately stop working (http//www.nhs.uk/conditions/Motor-neurone-disease/Pages/Introduction.aspx). This causes the muscles that the damage nerves supply to piecemeal lose strength, usually with wasting of muscles. It is ill-defined exactly what causes motor neurons to stop working, tho, there is non thought to be a link with factors like lifestyle, race and diet. In a elegant spell of cases (about 5%), there is a family history of both motor neuron disease or a related condition known as frontotemporal dementia. However, there is no single test to diagnose MND and diagnosing is solely based on the opinion of a neurologist, on the cornerstone of the symptoms observed and a physical examination. In few cases a specialise test is needed to rule out other possible conditions.Symptoms of motor neurone disease begin sluggishly over a period of weeks and months, generally provided on one side of the body at the beginning, and gradually get worse with time. Symptoms normally include having clumsy fingers or weaker wait (early signs of weakness). Other symptoms include wasting of muscles, muscle cr amps, hardships with swallowing and communication, excess saliva (difficulties swallowing saliva), and coughing later swallowing. After sometime, a person with motor neuron disease may find themselves unable to move. In a small number of cases (10-15%), motor neuron disease is associated with a type of dementia called frontotemporal dementia that atomic number 50 affect behaviour and personality.The main types of motor neuron disease are amyotrophic lateral sclerosis (ALS) (accounts for 60-70% of all cases), progressive bulbar palsy (PBP), progressive muscular atrophy (PMA), and primary lateral sclerosis (PLS) (http//www.patient.co.uk/health/Motor-Neurone-Disease).Spinal muscular atrophy (SMA) is an autosomal (a chromosome that is not allosome) recessive ancestral disease that causes muscle weakness and progressive privation of presence (http//www.fsma.org/FSMACommunity/understandingsma/WhatCausesSMA/). most 1 out of every 40 battalion are heritable carriers of the disease ( they carry the mutated gene but do not real have SMA) (http//www.fsma.org/FSMACommunity/understandingsma/WhatCausesSMA/). factor conversion is a permanent alteration in the DNA sequence that coifs up a gene (http//ghr.nlm.nih.gov/enchiridion/ editionsanddisorders/genemutation). Gene mutation occurs in two different ways they are either inherited from parents (known as hereditary mutation) or they are acquired at some time during a persons life (known as acquired mutation). contagious mutations happen when mutations are present in both the egg and spermatozoan cells. A person that has inherited this type of mutation has it present in virtually every cell in their body, without their lifetime. Acquired mutations occur in individual cells at some time during a persons lifetime. These changes disregard occur due to environmental factors like ultraviolet (UV) unprovoked from the sun, chemicals, and radiation, or if a mistake is made whilst DNA copies itself during cell variablen ess (mitosis and meiosis). Acquired mutations are only inherited if they occur in sex cells. jibe to the National Genome Institute, almost all diseases have some kind of genetical factor. These disorders send packing be cause by multiple gene mutations, a mutation in a single gene, combined gene mutation and environmental factors, or by chromosome damage or mutation. Gene mutation has been identified as the cause of legion(predicate) disorders including spinal muscular atrophy (SMA), haemophilia, Tay-Sachs, sickle cell, anaemia, cystic fibrosis and some cancers (http//biology.about.com/od/basicgenetics/ss/gene-mutation.htm).The term SMA is employ mainly for the most common form spinal muscular atrophy, which is caused by a genetic problem where one copy of the genetic error (mutation in autosomes) is inherited from each parent. SMA is classified into four different categories, from shell I IV. The classification of SMA depends on the age at which symptoms of the disease arise and the scratchiness of the symptoms. Symptoms of SMA normally include problems with breathing, eating, moving and swallowing floppy arms and legs (In children with either subject I or II SMA) twitching of the muscles in the arms, legs or tongue. Type I SMA is the most knockout, it mothers in babies under six months old. Type II is less severe that Type I SMA, it affects babies amidst the ages 6 to 18 months. Type cardinal and Type IV are the mildest types of SMA. Type III normally affects children around 3 years old. Type IV affects adults. In the most severe cases of SMA (Types I and II), fatal respiratory problems usually develop during childhood. In mild cases such(prenominal) as Types III and IV SMA, life expectancy is normally unaffected (http//www.nhs.uk/conditions/Spinal-muscular-atrophy/Pages/Introduction.aspx).Spinal muscular atrophy is caused by the deletion of the survival motor neuron gene 1 (SMN1) (http//www.fsma.org/FSMACommunity/understandingsma/WhatCausesSMA/ ). In healthy people SMN1 produces a protein known as the survival motor neuron (SMN) protein. In a person with mutated genes, the supply of this protein is absent or is significantly decreased. This results in the deterioration of the nerve cells (motor neurons) connecting the brain and spinal cord to the bodys muscles, therefore cavictimization muscle weakness and gradual loss of movement, because the SMN protein is critical to the survival and health of motor neurons. Spinal muscular atrophy affects 1 in 6000 to 1 in 10000 people.Myasthenia gravis is a unique long-term autoimmune condition which affects the nerves and muscles, resulting in the muscles becoming weak. An autoimmune condition is caused by the immune system mistakenly cominging and pulveriseing healthy body weave. Ordinarily, the immune systems white blood cells nurture the body from harmful substances, known as antigens. For examples viruses, bacteria, toxins, etc. antibodies are produced as a counter measure by the immune system that destroy the antigens. In people with autoimmune disorder, the immune system has difficulty distinguishing between antigens and healthy body tissue. Due to this an immune system response that kills healthy body tissue is produced. The cause of the immune system no longitudinal being able to distinguish between antigens and healthy body tissue is unknown at present. A theory suggests that drugs or microorganisms (like bacteria or viruses) may trigger some of these changes. In myasthenia gravis, the immune system accidentally produces antibodies (proteins) that damage or block muscle receptor cells. This clams muscles contracting because the antibodies prevent messages being past from the nerve endings to the muscles. However, it is not understand why the immune system of some people produce antibodies that attack the muscle receptor cells.Symptoms of myasthenia gravis generally include impaired warmness movement and weakness of muscles that are voluntarily controlled, therefore affecting functions such as facial expressions, eye and eye lid movement, chewing, talking and swallowing, and weakness of neck and limbs. However since weakness is a common symptom in many different diseases and conditions, diagnosing of myasthenia gravis is normally delayed or missed. Myasthenia gravis is diagnosed through Blood tests, Genetic tests and Electromyogram. In the U.S about 20 in 100,000 people are diagnosed with myasthenia gravis.Presently there is no known cure for MND, SMA, OR MG, however there are handlings that can be initiated with aims to ease symptoms to help the person feel more convenient and have a better quality of life, and compensate for the gradual loss of bodily functions like mobility, communication, breathing and swallowing. For example, for MND, muscle relaxants can help conquer muscle stiffness medicines such as phenytoin can hatch muscle cramps a breathing mask can help stiffen shortness of breath. Right now, the only ava ilable handling for MND that affects the progression of the disease is Riluzole, however it doesnt stop the progression of motor neuron disease, but only slows it down by a few months (http//www.nhs.uk/conditions/Motor-neurone-disease/Pages/Introduction.aspx). With SMA, depending on the severity, treatment could involve exercise, to prevent joint stiffness and improve range of movement and flexibility assistive equipment such as motorised wheelchairs and walking frames if mortal with SMA has difficulty moving nutrition advice and feeding tubes bracing and surgery to treat scoliosis (curvature of the spine) (http//www.nhs.uk/Conditions/Spinal-muscular-atrophy/Pages/Treatment.aspx). For patients with MG, medication such as pyridostigmine and neostigmine (less common), can prevent the dislocation of acetylcholine, an important chemical that assists the muscles in contracting (http//www.nhs.uk/Conditions/Myasthenia-gravis/Pages/Treatment.aspx). If pyridostigmine is ineffective, steroi d tablets can be used to lessen the symptoms. Doctors also often prescribe azathioprine, methotrexate or mycophenolate, to suppress the immune system. Muscle strength can be improve by controlling the production of abnormal antibodies through the use immunosuppressants. In some cases of MG, surgery to remove the thymus gland (a thymectomy) may be recommended. The thymus gland is part of the immune system and is found underneath the breast bone, it is sometimes abnormal in people with MG. In numerous cases, treatment of MG substantially improves muscle weakness allowing a person with the condition to lead a comparatively normal life. Some people may experience permanent or temporally periods where symptoms stop and treatment is no longer needed. Permanent remissions occur in about a third of the people who have a thymectomy (http//www.nhs.uk/Conditions/Myasthenia-gravis/Pages/Treatment.aspx).Currently, the hope of many is that stem cells of extraneural or neural origin might be modi fied in vitro (i.e. transforming skin cells into induced pluripotent stem cell (iPS)) (http//www.eurostemcell.org/factsheet/motor-neurone-disease-how-could-stem-cells-help) to differentiate into motor neurons that would transmigrate to sites of motor neuron loss and restore the motor pathways lost in MND by forming functional connections (Boulis, 2011). The most promising cells so far that can be used for stem treatment of MND are spinal cord stem cells, which are able to produce both motor neurons and a cell call glia. Many of the proteins known as growth factors that direct to motor neurons development are secreted by glia. There is also a possibility that non-neuronal cells such as glia can be used to prevent further damage to motor neurons and encourage repair through the production of the working version of the protein SOD1, which in some types of MND doesnt function properly (http//www.eurostemcell.org/factsheet/motor-neurone-disease-how-could-stem-cells-help). Stem cell the rapy also has to the potential to be used as a possible cure for SMA, MG and other neurological conditions.Gene therapy uses genes to prevent or treat a disease by introducing genetic material in cells to compensate for abnormal genes or to make a beneficial protein (MacKenzie, 2010). Gene therapy was found to be well meet as a future treatment for SMA by the Kaspar group who set forth a self-complementary (sc) AAV9 vector that crosses the blood-brain barriers after systemic administration because of scAAV9s rummy efficiency in central nervous system (CNS) gene transfer, after intravenous delivery in mice and other larger animals. Using this as a base, the Kaspar group along with Arthur burgees, detail the most successful extradite describe yet in a mouse model of severe SMA. This was achieved by injecting scAAV9 that is carrying SMN1, into the facial vein of mice pups on their sidereal day of birth (MacKenzie, 2010). The apostrophize of injecting scAAV9 into mice pups, resul ted in the transduction of 40% of motor neurons, and an extension of the lifespan of the mice from 2 weeks to more than 250 days, combined with almost normalised neuromuscular electrophysiology and normal motor function (MacKenzie, 2010).This forward data obtained in the gene therapy rescue of SMA in the mouse model, reported by the Kaspar group and Arthur Burghes (a pioneer of SMA), suggests that the same approach could be used in primates. The authors investigated systemic injection of scAAV9-GFP in a cynomolgus monkey (1 day of age). After four weeks, the magnitude of GFP in spinal motor neurons save was similar to that shown by the mice (MacKenzie, 2010), boding well for possible application to humans. This news, along with recent encouraging reports of AAV gene therapy of retinal disease, supports the further rehabilitation of gene therapy as a credible therapeutic alternative for neurological diseases, including MG, SMA and MND.The coif seems set with seemingly untreatable disorders of unknown pathogenesis an unknown presymptomatic way of diagnosis and, the small possibility of a cure through gene therapy and stem cell therapy, which are by far the best hopes, not only for MND, SMA and MG, but also for other neurological diseases. However, gene therapy and stem cell therapy are subject to a lot of public disagreement. For gene therapy this is due to fact that, gene therapy targeted at germ cells (egg and sperm cells), (known as germline gene therapy) could be pass on to next generations. Whilst it spares a family and their future generations from a specific genetic disorder, theres a possibility it could affect the development of a fetus in unexpected ways or have yet unknown long-term side effects (http//ghr.nlm.nih.gov/ vade mecum/therapy/ethics). Because the people who are going to be affected are not yet born, they are unable to choose whether to have the treatment, resulting in self-aggrandizing debates one whether germline gene therapy should b e used. Other good concerns involve banish impacts on what society thinks is normal, and discrimination toward those with the undesirable traits that arise from using gene therapy as a form modification for unwanted traits or to make genetic improvements. The idea of stem cell therapy is also controversial. Whilst it can used for the treatment of many diseases including neurological ones, there are ethical problems involving how it is obtained. For example, stem cells obtained from the embryo, because the embryo is viewed as a potential person. Due to this, victorious stem cells from an embryo is considered to be murder, however, its argued that, an early embryo that hasnt be implanted into the uterus doesnt have properties we associate with being a person, and therefore can and should be used for the benefit of patients (who are persons).Bibliographyhttp//ec.europa.eu/health/major_chronic_diseases/diseases/brain_neurological/index_en.htm (20/07/2014)http//www.nhs.uk/conditions/M otor-neurone-disease/Pages/Introduction.aspx (20/07/2014)http//www.patient.co.uk/health/Motor-Neurone-Disease (20/07/2014)http//www.fsma.org/FSMACommunity/understandingsma/WhatCausesSMA/ (04/07/2014)http//ghr.nlm.nih.gov/handbook/mutationsanddisorders/genemutation (20/06/2014)http//biology.about.com/od/basicgenetics/ss/gene-mutation.htm (21/06/2014)http//www.nhs.uk/conditions/Spinal-muscular-atrophy/Pages/Introduction.aspx (20/07/2014)http//www.nhs.uk/Conditions/Spinal-muscular-atrophy/Pages/Treatment.aspx (04/07/2014)http//www.nhs.uk/Conditions/Myasthenia-gravis/Pages/Treatment.aspx (21/07/2014)http//www.eurostemcell.org/factsheet/motor-neurone-disease-how-could-stem-cells-help (05/07/2014)Nicholas M. Boulis. (2011). Gene Therapy for Motor Neuron Disease.Gene Vector Design and Application to Treat Nervous System Disorders. 33 (3), p41-49Alex MacKenzie. (2010). A severe inherited neuromuscular disease is corrected in mice by intravenous gene delivery.Gene therapy for spinal muscular atrophy. 28 (3), 235-237http//ghr.nlm.nih.gov/handbook/therapy/genetherapy, (27/06/2014)http//ghr.nlm.nih.gov/handbook/therapy/ethics, (28/06/2014)http//ghr.nlm.nih.gov/handbook/therapy/procedures, (27/06/2014)