Light therapy has not yet been convincingly shown to help people with ALS. However, at specific wavelengths and energy densities, LT appears safe and has theoretically plausible mechanisms. There is a single case report suggesting benefits for light therapy in ALS, but it contains in sufficient detail to independently confirm diagnosis or treatment benefit. Further studies are needed to determine whether LT is useful for people with ALS, and via what specific protocols.
Pre-clinical models (animal or cell models recognized by ALSUntangled reviewers to be relevant to ALS)
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’.
Tamoxifen
Tamoxifen is reasonably safe, has plausible mechanisms for treating ALS, and has at least one positive preclinical study. One case report and 2 small human trials suggested an association between tamoxifen (at higher doses) and slower ALS progression but this is not enough evidence to recommend this medication as an ALS treatment. Moving forward, we would like to see a larger human ALS clinical trial of tamoxifen at 80mg daily. Interestingly, one study suggests that tamoxifen may decrease a person’s risk for getting ALS. We hope to see this independently replicated.
L-Carnitine
There are good theoretical mechanisms for carnitines, some pre-clinical evidence for
LC and ALCAR, and a single clinical trial that suggested ALCAR could slow disease progression in PALS. All three carnitines appear to be well-tolerated, generally safe, and inexpensive. We believe that there is a need for future clinical trials of carnitines in PALS to further elucidate their efficacy. Until there is further data, we cannot endorse any of these supplements as a definite way to slow ALS progression; however, oral ALCAR at 1000mg three times daily (3000 mg total daily dose) appears to be a theoretically promising supplement available for PALS whom would like to self-experiment.
Vitamin E
Vitamin E (a-tocopherol) is perhaps the most studied supplement in the history of ALS and was taken by one of the most famous ALS patients. Vitamin E has mechanistic potential in ALS as an antioxidant but appears in the SOD1 mutant mouse model to only have an effect on delaying disease onset. This bears out in human populations as large prospective cohorts show that long-duration vitamin E supplementation may decrease the risk of ALS, but randomized clinical trials show that even high dose vitamin E does not benefit the disease once ALS has been diagnosed. Although it is inexpensive and safe, we do not recommend vitamin E to slow, stop or reverse ALS
based on the lack of efficacy in clinical trials.
Glutathione
As an ALS treatment, glutathione and cysteine-containing supplements that increase glutathione appear reasonably safe, and they have a plausible mechanism, positive preclinical data and 2 interesting case reports. Unfortunately small clinical trials of glutathione itself and of acetylcysteine showed no significant benefit. Given these negative clinical trials, we do not advise PALS to take glutathione or cysteine-containing supplements for their ALS at this time.
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Perampanel
Perampanel is a drug currently used to treat seizures which has a mechanism of action that theoretically could be useful in treating patients with ALS. A single flawed study in a mouse model of ALS showed some benefits of perampanel, but data from humans with ALS is quite limited. Due to the lack of data in PALS, the failure of the closely related drug talampanel in ALS clinical trials, and several serious safety concerns, including an increased fall risk and serious psychiatric adverse effects, we cannot recommend off-label use of perampanel for ALS at this time. We look forward to the results of the on-going clinical trials of perampanel in ALS and we will update our TOE grades accordingly when these results become available.
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Antiretrovirals
Antiretrovirals are a group of diverse drugs developed for HIV infections that vary widely in theoretical efficacy against HERVs, side effect profiles, and cost. HERV expression is apparently increased in some PALS; however, it is unknown if this is a
beneficial, neutral, or pathological process. Furthermore, it is not clear if ARV-targeted mechanisms such as cell infection and viral replication are taking place in PALS. Based on the lack of evidence for use of ARVs in PALS who test negative for HIV and HTLV, we cannot recommend them as a treatment for ALS. We look forward to the results of the two ongoing trials of ARVs in PALS.
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Curcumin
Oral curcumin is safe, inexpensive, and has at least four potential mechanisms by which it might theoretically be useful in treating PALS. Flawed preclinical studies showed benefits of a curcumin chemical analog in a cell model of ALS, three PALS experienced validated motor improvements on regimens including curcumin (although there are several alternative explanations for these improvements) and there is one small pilot trial showing some benefit of curcumin in PALS. Based on the evidence presented in this review, some of us are planning a trial of Theracurmin at 90 mg twice daily in PALS.
Click here to download the complete review.