However, this calculation has been criticized for relying on an inappropriately low number of expected cases of ALS in the cohort. When the lifetime risk of developing ALS was used to predict the number of expected cases, soccer players were no more likely to die of ALS than the general population. Smoking
Smoking is possibly associated with ALS. A 2009 review concluded that smoking was an established risk factor for ALS. A 2010 systematic review and meta-analysis concluded that there was not a strong association between smoking and ALS, but that smoking might be associated with a higher risk of ALS in women. A 2011 meta-analysis concluded that smoking increases the risk of ALS versus never smoking. Among smokers, the younger they started smoking, the more likely they were to get ALS; however, neither the number of years smoked nor the number of cigarettes smoked per day affected their risk of developing ALS. Risk factor
ALS can strike at any age, but it increases with age. Most people who develop ALS are between the ages of 40 and 70, with an average age of 55 at the time of diagnosis. ALS is 20% more common in men than women, but the difference will disappear after age 70. It has also been suggested that military veterans are about 1.5 to 2 times more likely to develop ALS, though the reason is unclear.
Of the three, the fruit fly is the most widely used; it has a rapid life-cycle, short lifespan, a sophisticated nervous system, and many genetic tools available. C. elegans has a short life-cycle, is easy to manipulate genetically, and has a simple but well-understood nervous system. The zebrafish has transparent embryos that can be injected with DNA or RNA and has a lifespan of up to two years. Induced pluripotent stem cells (iPSCs) can be used to convert skin fibroblasts into motor neurons. It is now possible to generate iPSCs from people with ALS, which can then be converted into spinal motor neurons, which are useful for studying disease mechanisms and for testing potential drugs for ALS. iPSCs allow sporadic ALS to be modelled, which cannot be done with animal models. Treatments
From the 1960s until 2014, about 50 drugs for ALS were tested in randomized controlled trials (RCTs); of these, riluzole was the only one that showed a slight benefit in improving survival. Drugs tested and not shown to be effective in clinical trials in humans include antiviral drugs, anti-excitotoxic drugs, growth factors, neurotrophic factors, anti-inflammatory drugs, antioxidants, anti-apoptotic drugs, and drugs to improve mitochondria function.An analysis of 23 large phase II and phase III RCTs that failed between 2004 and 2014 concluded that there were many potential reasons for their lack of success. These trials in humans went ahead on the basis of positive results in SOD1 transgenic mice, which are not a good animal model for sporadic ALS.