Pyridostigmine enhances neuromuscular transmission and is commonly used to treat myasthenia gravis. The effect of pyridostigmine in slowing ALS progression is uncertain. Here we discuss the potential mechanisms, cases, clinical trial data, and potential risks.

Alpha-lipoic acid (ALA) is a naturally occurring fatty acid. It has several plausible mechanisms for slowing ALS progression. Preclinical studies showed ALA slowed motor function decline. Some patients reported improvement when taking ALA together with other supplements. Here we discuss the mechanism, clinical studies, and potential risks.

Paul Lingor, MD, is Professor for Neurology, Group Leader and Head of the Outpatient Clinics for Motoneuron Disorders and Co-head of the Outpatient Clinics for Movement Disorders and at the Department of Neurology of the TUM Klinikum Rechts der Isar in Munich, Germany.  Here he discusses the recent publication "Safety, tolerability, and efficacy of fasudil in amyotrophic lateral sclerosis (ROCK-ALS): a phase 2, randomised, double-blind, placebo-controlled trial."

Portable Neuromodulation Stimulator (PoNS) is a type of electrical stimulation that can theoretically increase rewiring in the brain (neuroplasticity).  Small trials suggest that it can improve walking in MS but thus far there are no data in people living with ALS.  Here we further discuss the mechanism, studies in other conditions, and potential risks.

ISRIB stands for “integrated stress response inhibitor).  As we discuss here, it is an oral medication that inhibits an intracellular pathway called the integrative stress response pathway.  It is not FDA approved for any condition but is available in Spain without a prescription.  There are theoretical ways that inhibiting this pathway could help a person with ALS, and there is promising data from preclinical ALS models.  However, it is not clear that ISRIB is soluble enough to get into motor neurons in the brain and spinal cord, and 2 of 3 trials of agents targeting the same pathway failed to show any benefits in people with ALS.  The risks of this product in ALS are not known.

Dr. Michael Benatar is a Professor of Neurology and Chief of the Neuromuscular Division and Executive Director of the ALS Center at the University of Miami. Here he discusses the recent publication “Proposed Research Criteria for Mild Motor Impairment as a Prodromal Syndrome in Amyotrophic Lateral Sclerosis."

Here we have a podcast produced by artificial intelligence discussing the recent publication “Design considerations for C9orf72 disease prevention trials”.

The Wahls Protocol is a diet that may reduce inflammation, oxidative stress, and mitochondrial dysfunction.  Although these are plausible mechanisms for slowing ALS progression, we discuss the fact that there are no actual data to support this hypothesis, and there are risks which are especially important to consider in people living with ALS.

Psilocybin is a psychedelic chemical derived from mushrooms.  It is under study for mood problems in people with ALS.  Here we review its plausible mechanisms for slowing ALS progression.  But there are no data from preclinical models, trials or case reports that currently support this benefit.  And there can be serious risks to using this chemical.

Here we review ashwagandha a nutritional supplement that has plausible mechanisms for slowing ALS, promising pre-clinical evidence, and a reasonable safety profile.  There is one person with ALS who experienced a reversal of symptoms on a cocktail of treatments that included ashwagandha.  Cases like this are difficult to interpret as there can be multiple explanations for a person experiencing an ALS reversal.  We have not found any other cases suggesting improvement on this product.  We hope to see the data from the completed phase 2 trial soon.