Updated May 4, 2026
As of May 4, 2026 we found new evidence of disrupted copper availability in spinal cords of people with ALS and ways this could contribute to the death of motor neurons https://pmc.ncbi.nlm.nih.gov/articles/PMC11267976/ . As a result, we upgrade our TOE Mechanisms Grade from B/C to A. We also found a paper describing some of the data from patients who were in the Copper ATSM trial. This showed no benefits https://pmc.ncbi.nlm.nih.gov/articles/PMC10947464/. While we wait for release of the full dataset, we thus change our TOE Trials Grade from U to F.
Key Information
Click on any letter grade below for more info:
Preclinical Trials Grade:
A
Published: Nov 2017
Copper dysregulation may play a role in ALS progression, particularly for the form caused by SOD1 mutations. Given the complexity of this problem, simple copper supplements are unlikely to be useful to PALS with normal serum copper levels. We do not recommend using these. CuATSM, on the other hand, has more promising potential mechanisms of action, and several positive pre-clinical studies in mutant SOD1 ALS models. There are even a small number of PALS reporting benefits from it, though in our opinion the described benefits are thus far of uncertain clinical significance. At this time, the safety of repeated doses of CuATSM is unknown, as is the optimum daily dose, and it appears to be very expensive. Until trials clarify dosing and safety, as well as effectiveness in patients with and without SOD1 mutations, we do not recommend using CuATSM for ALS.
Click here to download the complete review.
Grade A: Shown in a peer-reviewed publication to act on a relevant mechanism in humans
Grade B: Shown in a peer-reviewed publication to act on a relevant mechanism in pre-clinical model(s)
Grade C: Theoretically and plausibly acts on an ALS-relevant mechanism in humans
Grade D: Acts on a biological mechanism but it is not clear that this mechanism is relevant in ALS
Grade F: Implausible; would violate known principles or laws of biology
Grade U: No useful information was found for this category
Grade A: Two or more peer-reviewed publications reporting benefits in well-designed studies.
Animal studies are assumed to be ‘well designed’ when they follow published guidelines. When they deviate from these they are considered ‘flawed’.
Grade B: One peer-reviewed publication reporting benefits in a well-designed study.
Animal studies are assumed to be ‘well designed’ when they follow published guidelines. When they deviate from these they are considered ‘flawed’.
Grade C: One or more peer-reviewed publication(s) reporting benefits in flawed studies.
Animal studies are assumed to be ‘well designed’ when they follow published guidelines. When they deviate from these they are considered ‘flawed’.
Grade D: One or more non-peer reviewed studies reporting benefits (published on a website or in an abstract)
Grade F: The only studies available show no benefit
Grade U: No useful information was found for this category
Grade A: One or more peer-reviewed publications reporting benefits with validated diagnosis and benefits
Grade B: More than one unpublished report of benefit with validated diagnosis and benefits
Grade C: One unpublished report of benefit with validated diagnosis and benefits
Grade D: Subjective report(s) of benefit without validated diagnoses and/or benefits
Grade F: The only reports available show no benefit
Grade U: No useful information was found for this category
Two or more peer-reviewed publications describing benefits in well-designed randomized, blinded placebo-controlled phase III trials
Grade C: One or more peer-reviewed publications reporting benefits in a well-designed randomized, blinded, placebo-controlled phase I or II trial
Grade D: One or more peer-reviewed publications reporting benefits in a flawed trial.
Flawed trials means those in which there are identifiable problems with patient selection, randomization, blinding, controls or follow-up. These have ‘high or unclear risk of bias’ according to published criteria. Well-designed trials are those that have ‘low risk of bias’.
Grade F: The only trials available show no benefit
Grade U: No useful information was found for this category
Grade A: No exposed patients appear to have experienced harms
Grade B: More than 0% but less than 10% of exposed patients experienced harms (no hospitalizations or deaths)
Grade B (oral): More than 0% but less than10% of exposed patients experienced harms (no hospitalizations or deaths)
Grade D (intravenous): More than 0% but less than 5% of exposed patients experienced death or hospitalizations
Grade C: At least 10% of exposed patients experienced harms (no hospitalizations or deaths)
Grade D: More than 0% but less than 5% of exposed patients experienced death or hospitalizations
Grade D: More than 0% but less than 5% of exposed patients experienced death or hospitalizations
Grade F: At least 5% of exposed patients experienced death or hospitalization
Grade F: At least 5% of exposed patients experienced death or hospitalization
Grade U: No useful information was found for this category
Listen to the Podcast
Listen on Spreaker
