Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the death of motor neurons in the brain and spinal cord. ALS causes muscle stiffness, twitching, and weakness in its early stages. As the disease progresses, patients have difficulty speaking, swallowing, and breathing, in addition to body paralysis.

The U.S. Food and Drug Administration (FDA) approved three treatments to slow the progression of ALS: Rilutek (riluzole tablet), Tiglutik (riluzole suspension), and Radicava (edaravone). None of these treatments cures ALS, but when taken in combination with symptomatic treatments, they may improve patients’ quality of life and extend life expectancy.

Several experimental treatments are also being investigated to treat ALS. These include reldesemtiv (formerly known as CK-2127107) and cannabis.

Reldesemtiv

Reldesemtiv is a fast skeletal muscle troponin activator (FSTA) being developed by Cytokinetics in collaboration with Astellas Pharma. It is intended to slow down the rate of calcium release from the troponin protein complex, which regulates the contraction of sarcomeres (the fundamental units of muscle fibers). By increasing muscle contractility, reldesemtiv is expected to alleviate muscle weakness and fatigue in ALS patients.

A Phase 2, double-blind, randomized, dose-ranging, placebo-controlled, parallel group study of reldesemtiv (NCT03160898) called FORTITUDE-ALS was conducted in 458 patients in the U.S., Canada, Europe, and Australia. The trial did not show a statistically significant difference in slow vital capacity (SVC) — a measure of lung function — from baseline after 12 weeks of treatment, the primary endpoint. However, all patients on all doses of reldesemtiv showed improved SVC and ALS functional rating scale-revised (ALSFRS-R) compared to placebo-treated patients, with clinically meaningful differences emerging over time.

Cannabis

Preclinical data showed that cannabis has powerful antioxidant, anti-inflammatory, and neuroprotective effects that can prolong nerve cell survival, and delay the onset and slow the progression of the disease in ALS mouse models.

A randomized, double-blind, placebo-controlled crossover trial (NCT00812851) was conducted to determine the efficacy of orally administered tetrahydrocannabinol (THC) in 27 ALS patients who had moderate to severe daily cramps. The patients received 5 mg of THC twice a day for two weeks. Complete data were available for 22 patients. While THC was well-tolerated, the study showed no clinically significant difference between THC treatment and the placebo in the number and intensity of cramps.

A recent study published in The Lancet Neurology investigated whether cannabinoids (the active ingredient in cannabis) could reduce spasticity in ALS patients. This randomized, double-blind, placebo-controlled, Phase 2 study (NCT01776970) was conducted at four tertiary motor neuron disease centers in Italy. Sixty participants were randomly assigned to receive nabiximols (which contains cannabinoids) or a placebo for six weeks. The study showed that compared to the placebo, nabiximols had a positive effect on symptoms of spasticity. It also showed an acceptable safety and tolerability profile.

Currently, OMNI Medical Services is recruiting around 10,000 participants for a prospective observational study (NCT03944447) to determine the efficacy and safety of medical cannabis for a wide variety of chronic illnesses, including ALS. This study is expected to be completed at the end of December 2025.

Cann Trust is recruiting 30 participants at the Gold Coast Hospital and Health Service in Queensland, Australia, to conduct a randomized, double-blind, placebo-controlled Phase 3 trial (NCT03690791) to study the efficacy of cannabinoids in ALS. Patients will be treated with cannabis-based medicine extract or placebo for six months and evaluated for ALSFRS-R, forced vital capacity (FVC) — another measure of lung function — pain and spasticity score, and quality of life. The study is expected to be completed in January 2021.

Ilera healthcare, in collaboration with the Children’s Hospital of Philadelphia, is planning a prospective observational trial (NCT03886753) where patients with various diseases, including ALS, will be treated with one of four formulations of medical marijuana. The study aims to evaluate relief from primary disease symptoms after treatment for one year along with any associated side effects. It will also evaluate the pharmacokinetic parameters such as the amount of treatment in the blood, the rate of absorption of the treatment by the body’s circulatory system, the metabolic parameters or the half-life of the treatment, and the non-toxic therapeutic dose range of the treatment. The study has not yet started recruiting.

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