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.
If people with ALS or their family members are reluctant to discuss end-of-life issues, it may be useful to use the introduction of gastrostomy or noninvasive ventilation as an opportunity to bring up the subject.Hospice care, or palliative care at the end of life, is especially important in ALS because it helps to optimize the management of symptoms and increases the likelihood of a peaceful death. It is unclear exactly when the end-of-life phase begins in ALS, but it is associated with significant difficulty moving, communicating, and, in some cases, thinking. Although many people with ALS fear choking to death (suffocating), they can be reassured that this occurs rarely, about 0–3% of the time. About 90% of people with ALS die peacefully. In the final days of life, opioids can be used to treat pain and dyspnea, while benzodiazepines can be used to treat anxiety. Epidemiology
ALS is the most common motor neuron disease in adults and the third most common neurodegenerative disease after Alzheimers disease and Parkinsons disease. Worldwide the number of people who develop ALS yearly is estimated to be 1.9 people per 100,000 per year, while the number of people who have ALS at any given time is estimated to be about 4.5 people per 100,000. In Europe, the number of new cases a year is about 2.6 people per 100,000, while the number affected is 7–9 people per 100,000. The lifetime risk of developing ALS is 1:350 for European men and 1:400 for European women.