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.
Patient case reports
Acetyl-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.
RCH4
RCH4 is an unlicensed, unapproved product reported to “probably slow the progression of your ALS” (6) on a website. The only peer reviewed publication we found on this product is a single abstract which was never presented at a meeting. We have been unable to determine RCH4’s structure or chemical class, and its purported mechanism is one that has never been shown to be useful in treating PALS before. We have been unable to independently verify RCH4’s reported efficacy or even safety. Thus, at this time, we cannot advise PALS to use this product. We hope the proponents of RCH4 will someday present more useful information about their product at a scientific meeting or in a peer reviewed publication.
We believe that regulatory oversight is important for optimizing patient safety on experimental drugs, and that independent peer review and replication are fundamentals of good science. Caution should be exercised around any product being developed and in clinical use without these safeguards and fundamentals in place.
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Resveratrol
Resveratrol is a dietary supplement that likely activates SIRT1 cellular pathways and may alter the gut microbiome. These are interesting mechanisms that may potentially alter the progression of ALS and do confer benefit in animal models of one type of familial ALS; however, to-date, there have been no trials of resveratrol in PALS. Some trials in other populations show frequent gastrointestinal adverse events, including weight loss, and one trial showed a high risk of serious renal toxicity. Given the unknown benefit of resveratrol in PALS and the possible risks, we cannot recommend resveratrol as an ALS treatment at this time. We hope to see well-designed clinical trials of resveratrol and other SIRT1 modulators in the near future.
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Hyperbaric Oxygen
Although there are plausible mechanisms by which HBOT could work in ALS and a flawed pre-clinical study showing benefit in a mouse model, the best available human trial of HBOT showed no benefit. Given this negative human trial and the fact that HBOT has potentially serious complications, we do not recommend HBOT for patients with ALS at this time.
Kim Cherry’s ALS reversal, which occurred on HBOT and several other alternative treatments, appears very interesting. We do not think this is due to HBOT alone. There are other rare examples of ALS reversals on different (or sometimes no) treatments (28). Other explanations for these reversals include undetected ALS mimics syndromes or endogenous mechanisms that confer resistance to the disease (28). We look forward to further study of cases like this (29).
Declaration of interest: ALSUntangled is sponsored by the ALS Association and the Motor Neurone Disease Association.
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Accilion
In our opinion, Accilion does not have a mechanism that is plausible for the treatment of ALS. There is one patient with a confirmed diagnosis of slowly progressive ALS who had modest objective improvements in motor function while using Accilion. However, improvements such as these have been described before, even in patients taking a placebo (32). We believe improvements in PALS are important to study, but they may have multiple explanations and thus are not proof of treatment efficacy (32). At this time we do not recommend the use of Accilion for ALS.
Declaration of interest: ALSUntangled is sponsored by the ALS Association and the Motor Neurone Disease Association.
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Protandim
Protandim appears reasonably safe and inexpensive, has a promising mechanism by which it could help ALS, and there is a patient with a validated ALS diagnosis whose ALSFRS-R score improved on it. There are significant problems with the data described, including small study sample sizes, failure to demonstrate that Protandim increases Nrf2 in humans, failure to establish an optimal dose, and potential conflicts of interest among several of the key individuals involved. Nonetheless, in our opinion, further study of Protandim in ALS appears warranted.
Declaration of interest: ALSUntangled is sponsored by the ALS Association and the Motor Neurone Disease Association.
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Lunasin
Lunasin has interesting mechanisms of action that might be useful in treating ALS, and it appears reasonably safe although some forms of it are expensive. While some PALS have reported improvements on lunasin, we have thus far found only one in which we were able to independently validate these improvements. This patient had atypical features for ALS including a history of myasthenia gravis, which can produce weakness that improves spontaneously. At this time there is not enough evidence to recommend that PALS take lunasin. A reasonable next step would be a small pilot trial of lunasin with validated ALS diagnoses and outcome measures.
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