However, many drug targets that were shown to be effective in the SOD1G93A transgenic mouse failed in clinical trials in humans; other SOD1 models have had similar problems. Most of these drugs were identified as potentially effective based on a single study in a rodent SOD1 model and then failed in clinical trials in patients who primarily had sporadic ALS. It is thought that these clinical trials failed because SOD1 mutations account for only 2% of all ALS cases and because the pathology of SOD1 ALS is thought to be distinct from all other types of ALS; it lacks the abnormal aggregations of TDP-43 protein or FUS protein seen in nearly all other cases of ALS.As of 2018, there are about 20 TARDBP mouse models, a dozen FUS mouse models, and a number of C9orf72, PFN1, and UBQLN2 mouse models. There are also new methods of developing animal models, including viral transgenesis, in which viruses are used to deliver mutant genes to an animal model, and CRISPR/Cas9, which can be used to give an animal model multiple mutated genes. Both of these methods are faster and cheaper than traditional methods of genetically engineering mice; they also allow scientists to study the effects of a mutation in mice of different genetic backgrounds, which better represents the genetic diversity seen in humans.Cellular models used to study ALS include the yeast Saccharomyces cerevisiae and rat or mouse motor neurons in culture. Small-animal models include the fruit fly, the roundworm C. elegans, and the zebrafish.
Attitudes toward invasive ventilation vary from country to country; about 30% of people with ALS in Japan choose invasive ventilation, versus less than 5% in North America and Europe. Therapy
Physical therapy plays a large role in rehabilitation for individuals with ALS. Specifically, physical, occupational, and speech therapists can set goals and promote benefits for individuals with ALS by delaying loss of strength, maintaining endurance, limiting pain, improving speech and swallowing, preventing complications, and promoting functional independence.Occupational therapy and special equipment such as assistive technology can also enhance peoples independence and safety throughout the course of ALS. Gentle, low-impact aerobic exercise such as performing activities of daily living, walking, swimming, and stationary bicycling can strengthen unaffected muscles, improve cardiovascular health, and help people fight fatigue and depression. Range of motion and stretching exercises can help prevent painful spasticity and shortening (contracture) of muscles. Physical and occupational therapists can recommend exercises that provide these benefits without overworking muscles, because muscle exhaustion can lead to worsening of symptoms associated with ALS, rather than providing help to people with ALS. They can suggest devices such as ramps, braces, walkers, bathroom equipment (shower chairs, toilet risers, etc. ), and wheelchairs that help people remain mobile. Occupational therapists can provide or recommend equipment and adaptations to enable ALS people to retain as much safety and independence in activities of daily living as possible. Since respiratory insufficiency is the primary cause of mortality, physical therapists can help improve respiratory outcomes in people with ALS by implementing pulmonary physical therapy.