Lou+Gehrig's+Disease

=Amyotrophic lateral Sclerosis(ALS) =

Amyotrophic lateral Sclerosis(ALS) or Lou Gehrig’s Disease
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Root causes of the disease:
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 * The cause of the disease is unknown but it is thought that the autosomal dominant ALS gene is inherited, or sporadically mutated.
 * Only about 5 to 10 percent of cases are due to inheritance.
 * In 1993, Rosen et al.described mutations in the gene encoding superoxide dismutase 1 (SOD1) that account for 20 percent of cases of familial ALS. SOD1 encodes for 153 amino acids and forms a subunit of a Copper catalytic ion and a Zinc stabilizing ion. Though non covalent bonding, pairs of these subunits form SOD1 homodimers. The precise toxic function of the SOD1 mechanism is still unknown, although there are a number of hypotheses: Zinc deficiencies in the superoxide anion cause the copper to participate in the creation of peroxynitrile, and other toxic oxidation reactions that harm the neurons. Lastly, the selective loss of glial glutamate transporters overtime can lead to the formation of ALS.
 * A number of other genes have been identified in the susceptibility or cause of ALS. A mutation in the SOD1, FUS, and TARDBP genes explain 25-35% of the familial cases.
 * The remaining 80 percent are caused by mutations in other genes. Another autosomal dominant form of ALS progresses slowly and begins before the age of 25 years; the gene has been mapped to chromosome 9q34.
 * The gene for ALS with frontotemporal dementia has been mapped to 9q21–22. Autosomal recessive juvenile-onset ALS has been linked to chromosomes 2q33 and 15q15–22. These are the only confirmed links to ALS and there are various speculations about heavy metals and exposure to retro viruses.

What parts of the body does the disease effect?
====Amyotrophic lateral sclerosis causes the degeneration and loss of motor neurons with astrocytic gliosis which starves muscle cells and causes muscles to atrophy. ==== = =

Historical background of the disease:
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 * 1) Earliest descriptions of ALS were in the 1800s, when Aran reported 11 cases of weakness, including a 43 year old man and three of his blood relatives, whom all died of a familiar disease.
 * 2) In 1824 Charles Bell wrote the first report about amyotrophic lateral sclerosis (ALS).
 * 3) In 1869 the Franch doctor Jean-Martin Charcot was the first to describe ALS in scientific literature.
 * 4) In 1850 the first description of shriveled nerve fibers was made by Augustus Waller.
 * 5) <span style="font-family: 'Times New Roman',Times,serif; font-size: 16px;">In 1939 the disease becomes very well known when the baseball legend, Lou Gehrig, is diagnosed with ALS. He was diagnosed on July 4, 1939 and died nearly two years later on July 2, 1941. The attention he brought to the disease and its seriousness has it as honorary name after him.
 * 6) <span style="font-family: 'Times New Roman',Times,serif; font-size: 16px;">In the 1950’s an ALS epidemic occurred in Guam. The area of Guam inhabited by the Chamorro people, who have historically had a high incidence (as much as 143 cases per 100,000 people per year) of a condition called Lytico-Bodig disease which is a combination of symptoms similar to ALS, parkinsonism, and dementia. Two more areas of increased incidence are West Papua and the Kii Peninsula of Japan.
 * 7) <span style="font-family: 'Times New Roman',Times,serif; font-size: 16px;">Most notably is Stephan Hawking’s diagnosis of ALS in 1962 at the age of 21. The successful theoretical physician has lived with the disease for more than 50 years, an exceptional case of this disease. The progression of his disease continues to this day. He uses a computer program called the "Equalizer" which he received from Walt Woltosz. He uses this method to this day, using a switch he selects phrases, words or letters from a bank of about 2500–3000 that are scanned. The program was originally run on desktop computer; however, a computer engineer adapted a small computer and attached it to his wheelchair.
 * 8) <span style="font-family: 'Times New Roman',Times,serif; font-size: 16px;">In 1993 the SOD1 gene on chromosome 21 was found to play a role in some cases of ALS and then.
 * 9) <span style="font-family: 'Times New Roman',Times,serif; font-size: 16px;">In 1996 Rilutek was the first FDA approved drug for ALS, increasing the lifespan of those affected for a few months and giving them a longer period of functioning motility. It did this by lowering glutamate levels, glutamate causes nerve damage in the brain.
 * 10) <span style="font-family: 'Times New Roman',Times,serif; font-size: 16px;">In 1998 the El Escorial criteria was developed as the standard for classifying ALS patients.
 * 11) <span style="font-family: 'Times New Roman',Times,serif; font-size: 16px;">Recently, in 2011 the noncoding repeat expansions in C9ORF72 were found to be a major cause of ALS and frontotemporal dementia.

<span style="font-family: 'Times New Roman',Times,serif; font-size: 20px; vertical-align: baseline;">Symptoms of the disease include:

 * ====<span style="font-family: 'Times New Roman',Times,serif; font-size: 16px;">muscle weakness in one or more of the following: hands, arms, legs or the muscles of speech, swallowing or breathing ====
 * ====<span style="font-family: 'Times New Roman',Times,serif; font-size: 16px;">twitching (fasciculation) and cramping of muscles, especially those in the hands and feet ====
 * ====<span style="font-family: 'Times New Roman',Times,serif; font-size: 16px;">impairment of the use of the arms and legs ====
 * ====<span style="font-family: 'Times New Roman',Times,serif; font-size: 16px;">"thick speech" and difficulty in projecting the voice ====
 * ====<span style="font-family: 'Times New Roman',Times,serif; font-size: 16px;">in more advanced stages, shortness of breath, difficulty in breathing and swallowing ====

<span style="font-family: 'Times New Roman',Times,serif; font-size: 20px;">Standard treatments include:

 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 16px;">Riluzole (Rilutek) is the only treatment that has been found to improve survival but only to a modest extent of around a few months. It also extends the time before a person needs ventilation support. Riluzole does not reverse the damage already done to motor neurons, and people taking it must be monitored for liver damage which occurs in about 10 percent of the people taking the drug. It is approved by Food and Drug Administration (FDA) and recommended by the National Institute for Clinical Excellence (NICE).
 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 16px;">Another method of treatment is disease management where the patient is kept as comfortable and motile as possible. Sometimes there are pharmaceutical treatments where medical professionals can prescribe medications to help reduce fatigue, ease muscle cramps, control spasticity, and reduce excess saliva and phlegm. Drugs also are available to help patients with pain, depression, sleep disturbances, dysphagia, and constipation.
 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 16px;">Certain treatment facilities also offer speech therapy, feeding and nutrition help and breathing support in later stages of the disease. There is also palliative care for patients who need in home nurses and caregivers.

<span style="font-family: 'Times New Roman',Times,serif; font-size: 20px; line-height: 1.5;">Current research:
====<span style="font-family: 'Times New Roman',Times,serif; font-size: 16px; line-height: 1.5;">Research on ALS is genome centered, and geneticists are trying to locate more genes responsible for ALS. Repeats in GGGGCC nucleotides have been found in patients with ALS and frontotemporal dementia (FTD), but the incidence of this is very rare (Konno et al 2013). Mutations in the SQSTM1 gene have been identified as a possible cause of ALS due to the increasing incidence of mutations located in the ubiquitin associated domain of the p62 protein in ALS patients (Teyssou et al 2013). Researchers at UC San Diego are developing an ALS therapy involving human embryonic stem cells used to create astrocyte precursors that would be transplanted in to patients, in hopes of maturing into new astrocytes and reversing the degenerative effects of ALS. Gene silencing and gene therapy are new treatments that have been in tested in clinical trials since 2010, an antisense drugs was made to silence the SOD1 gene in familial ALS patients. ====

<span style="font-family: 'Times New Roman',Times,serif; font-size: 20px; line-height: 1.5;">References:

 * ====<span style="font-family: 'Times New Roman',Times,serif; font-size: 16px; line-height: 1.5;">Andersen PM, Sims KB, Xin WW, Kiely R, O’Neill G, Ravits J, Pioro E, Harati Y, Brower RD, Battistini S., Benigni M., Ricci C., and Rossi A. SOD1 Mutations in Amyotrophic Lateral Sclerosis EUROPEAN NEUROLOGICAL JOURNAL ====
 * ====<span style="font-family: 'Times New Roman',Times,serif; font-size: 16px; line-height: 1.5;">Kunst C. 2004. Complex Genetics of Amyotrophic Lateral Sclerosis. American Journal of Human Genetics 75:933-947 ====
 * ====<span style="font-family: 'Times New Roman',Times,serif; font-size: 16px; line-height: 1.5;">Konno T, Shiga A, Tsujino A, Sugai A, Kato T, Kanai K, Yokoseki A, Eguchi H, Kuwabara S, Nishizawa M, Takahashi H, Onodera O. (2013) Japa <span style="font-family: 'Times New Roman',Times,serif; font-size: 16px;">nese amyotrophic lateral sclerosis patients with GGGGCC hexanucleotide repeat expansion in C9ORF72. ====
 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 16px;">Rowland, Lewis P., and Neil A. Shneider. "Amyotrophic Lateral Sclerosis." New England Journal of Medicine 345.15 (2001): 1131-1132. Print.
 * ====<span style="font-family: 'Times New Roman',Times,serif; font-size: 16px;">Teyssou E, Takeda T, Lebon V, Boillée S, Doukouré B, Bataillon G, Sazdovitch V, Cazeneuve C, Meininger V, LeGuern E, Salachas F, Seilhean D, Millecamps S. (2013) Mutations in SQSTM1 encoding p62 in amyotrophic lateral sclerosis: genetics and neuropathology. Acta Neuropathol. 125:511-22 doi: 10.1007/s00401-013-1090-0 ====
 * ====<span style="font-family: 'Times New Roman',Times,serif; font-size: 16px;">"Current Projects in ALS & Motor Neuron Disorder Research." Lou Geh <span style="font-family: 'Times New Roman',Times,serif; font-size: 16px; line-height: 1.5;">rig's Disease and ALS Research at UC San Diego. N.p., n.d. Web. 1 Dec. 2013. <http://als.ucsd.edu/research/Pages/current-projects.aspx>. ====