DECEMBER 202319smoking has also been reported to increase the risk of ALS. Metals have been thought to be associated with ALS and studies suggest that cadmium, lead, mercury, manganese, and zinc could contribute to ALS etiology. Solvents such as methylene chloride have been proposed to potentially be associated with an increased risk of ALS. Radiation can cause an accumulation of misfolded proteins which could lead to neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and ALS. There have been some theories suggesting that there is an increased risk of ALS comorbid with an occupation that involves high intensity physical activity. Professional athletes may be exposed to pesticides, thus increasing the risk of ALS. In addition to general pesticide exposure can increase the risk of ALS, specific pesticides include organochlorine, aldrin, dieldrin, DDT, and toxaphene. Viruses that have been associated with ALS include poliovirus, coxsackievirus, echovirus, enterovirus A71, SARS-CoV-2, and enterovirus D68. There has been compelling evidences of fungal infection in patients with ALS with previous reports of yeast and hyphae in their motor cortex, medulla, and spinal cord.. Candida, Malassezia, Fusarium, Botrytis, Trichoderma, and Cryptococcus have also been found in frozen neural tissue of ALS patients. Of note, there was no significant association between alcohol consumption and ALS in previous studies. Currently clinical trials for ALS involve the following: · Perampanel/telampanel (AMPA receptor agonist used in Parkinson's disease)· AMX0035 (reduces mitochondrial dysfunction)· Oxaloacetic acid (reduces inflammation and promotes neurogenesis)· Bosutinib (tyrosine kinase inhibitor)· Zilucoplan (inhibits membrane attack complex)· Nicotaniamide (neuroprotective)· Trametinid (decreases cell proliferation)· Mastinidb (tyrosine kinase inhibitor)· Anx005 (binds and blocks complement activity, which can keep synapses healthy)· RAPA 501 (reprogrammed T cells)· AP-101 (monocolonal antibody that targets the abnormal misfolded SOD1)· MN-166 (neuroprotective by inhibiting proinflammatory cytokines)· Lenzumestrocel (stem cell therapy)· Dazucorilant (Glucocorticoid receptor antagonist)· SAR443820 (RIPK1 inhibitor, currently enrolling at AdventHealth Orlando)· PTC857 (inhibits enzyme important for oxidative stress)· Barcitinib (JAK1 inhibitor, reduces inflammation)· Prosetin (reverses cell endoplasmic reticulum stress)· Monepantel (reduces protein accumulation)Current medications given for ALS: Radicva (Edaravone), Rilutek (Riluzole), Relyvrio (Edaravone), Qalsody (Toferson)Current devices for ALS : motorized wheelchair, eye gaze devices, ventilator, reachers, dressing aids, zipper pullers, door openers, lamp switches, key turners, pill dispensers, bathing tools, special utensils, and kitchen aids to help open jars, shower chair, bedpans, toilet seats, transfer benches, handheld showers, grab bars, hospital beds, over bed tables, patient lifts, bedside commodes, trapeze bars, lift chairs, safety rails, canes, quad canes, forearm crutches, walkers, rollators, manual wheelchairs, transport wheelchair, lightweight wheelchair, power wheelchair, scooters, oxygen, cpap, bipap, and ventilators. Conclusion: Although there are genetic causes of ALS, the sporadic causes of ALS are unknown. Further investigation into the risk factors of ALS could help solve this neuroscience mystery. The problem with ALS is that there are multiple potential etiologies and no cure yet
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