Looking Back and Looking Forward at Stuff

Background: Amyotrophic lateral sclerosis (ALS) is a terminal condition, which is increasing in incidence. Therapeutic interventions have enjoyed limited success. However, research is progressing, with some promising drug candidates emerging. Patients cannot always wait for the results of large trials. The general practitioner has a central role in management of ALS. Objective: To review and summarise available evidence evaluating the disease-modifying and life-extending potential of approved medications available off-label or over the counter. To inform doctors and patients of updates in the field and assist their decision-making. Method: A literature search was conducted of PubMed, UpToDate and Google Scholar from 1st January 2010 until 1st July 2020. Search terms were “amyotrophic lateral sclerosis”, “motor neuron(e) disease”, “clinical trial”, and “treatment”, with review articles and clinical trial results evaluated by the author for safety and efficacy. Only literature investigating medications already approved for use in Australia was included. Discussion: Four experimental candidates were deemed to have a reasonable likelihood of efficacy, and doses/routes of administration were clarified. Possibilities for novel therapies were outlined, and the importance of research support was highlighted. Introduction A 65-year-old woman presented to her general practitioner (GP) with foot drop. Neurological examination and neurophysiological studies confirmed sporadic amyotrophic lateral sclerosis (ALS), a terminal condition. Two Australian patients receive this diagnosis daily (1). She was offered standard treatment, including riluzole and medications to relieve symptoms. She sought further therapeutic options in concert with her treating team, but found no clear source of research updates. Aim Advances in ALS have been limited. There is some optimism at present, which has not been widely reported. This article presents news of current research into potentially useful disease-modifying and life-extending treatments for this condition, to inform GPs and patients. In particular, evidence for off-label prescribing of approved medications, and over-the-counter medications/ supplements, is examined. While robust randomised controlled trials with hundreds of participants provide the strongest evidence of efficacy, ALS patients often cannot wait for these results. There is therefore more freedom applied to the therapies discussed, following demonstration of an adequate safety profile. However, medications are still assessed with reference to available evidence. This article does not outline ongoing clinical trials, as these are changing rapidly. Also, it does not focus on standard treatment, which is covered elsewhere (2). The treatments discussed in this paper are experimental. This information must be handled with caution and used only in consultation with a neurologist. No assurance is offered that use of these medications for this condition is safe or appropriate for any particular patient. Off-label prescribing remains the responsibility of the prescriber, and treatments should be added in a stepwise fashion to allow observation of benefit and/or side effects. Clinicians should be aware of the limitations of trials with small patient numbers (for example, Phase II trials), even if they show a statistically significant effect. [Lithium (3) and dexpramipexole (4), though initially promising in ALS, were shown to be ineffective in trials with larger patient numbers. ]