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.
Risks (harms that occurred on this treatment)
Azathioprine
As an immunosuppressant drug, AZA has a plausible mechanism for slowing the progression of ALS. However, there is no pre-clinical data to support its use and two clinical trials did not support efficacy. There are 2 published cases in which
ALS reversals occurred on AZA, but it is not clear to us that the AZA actually contributed to the ALS improvements. One of these patients also had myasthenia gravis, which is known to cause reversible weakness and therefore complicates the measurement of ALS. The other patient was taking many different medications and supplements along with AZA. AZA has very serious, potentially fatal, both short and long-term risks associated with its use and requires medical monitoring. Based on the
available data, we do not advise the use of AZA as an ALS treatment
LEAP2BFIT
Many ingredients contained within LEAP2BFIT could, at least in theory, be beneficial in ALS. Some of these ingredients have supporting animal or human studies. However, it is unknown if these ingredients are being provided in therapeutic quantities since the dosages are not disclosed. Furthermore, it is impossible to know the net positive or negative effect of so many ingredients without carefully testing the combination. Based on the above discussions, we do not currently recommend LEAP2BFIT as a way to slow, stop, or reverse ALS.
Vinpocetine
Vinpocetine has several plausible mechanisms by which it could slow ALS progression. There are two PALS online who reported improved motor functions on supplement cocktails containing Vinpocetine, but many other PALS have had no
benefits. Serious side effects from Vinpocetine are rare and it is inexpensive. We support further study of Vinpocetine in ALS, but our group was split on what the next step should be; some were in favor of a study in a pre-clinical ALS model and others were in favor of a small human trial to confirm its benefit on cramps (7) and to explore whether it is safe, tolerable and might slow disease progression.
Penicillin G/Hydrocortisone
In our opinion, there is no convincing evidence that GABA overload plays a role in ALS progression. PNG/HC has other theoretical mechanisms by which it could slow ALS progression, but previous human trials involving steroids and a trial of a b lactam with more potent effects on glutamate did not help. We have not been able to confirm the diagnoses, nor the improvements described in the case series of 3 PALS taking PNG/HC; however, even if these treatment effects were real, these improvements were transient and quickly became unresponsive to treatment. Unless the ongoing placebo-controlled trial shows objective and sustained clinical improvements, we do not recommend that PALS take this expensive and risky combination of penicillin G and hydrocortisone.
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Copper
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.
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Eric is Winning
In conclusion, we find few plausible mechanisms by which components of the EIW regimen might impact ALS progression, and no pre-clinical or clinical evidence to support using this complicated, expensive and potentially risky treatment. Mr. Edney appears to have had very slow ALS progression even before he started his protocol, and there is no convincing evidence that the EIW regimen slowed, stopped or reversed his disease.
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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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