Amyotrophic Lateral Sclerosis

Both symptoms-relieving therapy and disease-modifying are available, as well as new therapeutic options.

Amyotrophic lateral sclerosis (ALS) is a terminal neurological illness that begins with weakness in the limbs and progresses to dysarthria, dysphagia, and dyspnea. Pseudobulbar affect, sialorrhea, tiredness, spasticity, cramping, and weakness are just a few of the distressing symptoms. Death usually occurs 2 to 5 years after the beginning of symptoms, and is caused by a decrease in swallowing and breathing. The loss of central and peripheral motor neurons causes symptoms. The actual pathophysiology of ALS is still being researched, and the illness is complicated, with numerous theories offered. There is no cure; however, the Food and Drug Administration (FDA) has authorized two disease-modifying therapies (DMTs) that reduce disease development but do not enhance strength or function. A variety of medicines are also used to treat particular symptoms, frequently without an FDA-approved indication (i.e. “off label”). Clinical studies are underway for a number of potential therapeutic medicines, some of which have shown encouraging results. This article explores developing therapy options and reviews existing medicines to halt disease development and lessen symptom severity.

Pathophysiology

The aggregation of proteins, particularly the TAR DNA binding protein 43, is a plausible explanation for the genesis and development of the ALS disease process (TDBP43).
Another prominent theory argues that aberrant increases in reactive oxygen species arise, causing the cells to be injured. 4 Excess glutamate-induced excitotoxicity, immune-mediated inflammatory responses, and mitochondrial dysfunction linked to superoxide dismutase 1 (SOD1) mutations are among the other possibilities. These ideas are not mutually exclusive, and various variables, possibly both genetic and environmental, are likely to have a role.

Approved Disease-modifying Treatment

Riluzole. Riluzole, a glutamate inhibitor, has been demonstrated to have a neuroprotective effect, most likely by reducing glutamate transmission and inhibiting harmful excess glutamate. Riluzole was authorized after a randomized clinical trial revealed that riluzole had a considerably better 1-year survival rate (74%) than placebo (58 percent). 5 Additional trials verified the efficacy of riluzole in increasing 1-year survival rates and determined that 100 mg daily in two 50-mg doses is the optimum therapeutic dosage. 1 Fatigue, dizziness, and gastrointestinal problems are the most frequent side effects (eg. nausea, abdominal pain, or diarrhea). These effects may disappear if the dosage is reduced to 50 mg once a day. Riluzole can cause increased liver enzymes, which usually return to normal after the drug is stopped, and in rare circumstances, neutropenia.

Edaravone. Approved in 2017, edaravone is expected to alleviate ALS development by neuroprotective removal of free radicals. 4 Although it should be noted that this benefit occurred specifically in participants who were in the early stages of ALS, and edaravone efficiency will decrease as the ALS progresses, edaravone treatment resulted in significantly lower declines on the revised ALS functional rating scale (ALSFRS-R) compared to placebo in clinical trials. 4 Edaravone is given intravenously in the regular doses of 60 mg spread out over an hour. The treatment starts with 14 days of daily infusions, followed by 14 days without treatment, and then 10 days of infusions every month (which may be split into 5 days, 2 days off, and then another 5 days). Bruising at the injection site, headaches, and gait abnormalities are all possible side effects. Thrombosis, bleeding, and infection are among the possible complications with intravenous administration systems (such as port-a-caths and central lines). Most insurance providers in the United States have a stringent set of reimbursement requirements for edaravone medication that closely resembles the clinical trials enrollment criteria.