ALS Untangled®

ALSUntangled® reviews alternative and off label treatments (AOTs), with the goal of helping people with ALS make more informed decisions about them.

Patient case reports

Ayahuasca

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Ayahuasca has interesting mechanisms that could potentially be useful in treating human ALS. We found one person who appears to have experienced an ALS reversal following exposure to a single dose of ayahuasca and several other AOTs. We do not believe that a single dose of ayahuasca could trigger a mechanism that would reverse ALS. There are more plausible explanations for this case, including an unrecognised ALS mimic syndrome. Importantly, there are several documented harms associated with ayahuasca use, including hospitalisation, intubation, and death. There are also serious theoretical risks, including hypertensive crisis, serotonin syndrome, and birth defects. Given this information, at this time, we do not endorse the use of ayahuasca to slow, stop or reverse ALS progression.

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Inosine

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Inosine is a low-cost supplement that increases the levels of urate, a naturally occurring antioxidant. With appropriate blood and urine monitoring, it appears reasonably safe. Epidemiologic data suggest that high urate levels may be associated with improved survival in ALS, which prompted preclinical studies and clinical trials of inosine. These are still ongoing and will help determine whether inosine could be a useful treatment for ALS.‌

Declaration of interest: ALSUntangled is sponsored by the ALS Association and the Motor Neurone Disease Association.

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GM604

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At this time ALSUntangled finds no independently verifiable data supporting the efficacy or even the safety of GM604 in patients with ALS. We believe that independent peer review and replication are fundamentals of good science (36,37). Accordingly, we share the FDA’s April 2015 opinion that the data on GM604 in ALS should be released now for

independent peer review (38). If these preliminary data are confirmed to be positive, statistics on the false-positive rate of small trials (29,30) and consensus ALS trial guidelines (35) dictate that they be replicated in a larger, longer duration study before GM604 is deemed effective or even safe for patients with ALS.‌‌

ALSUntangled generally supports the use of expanded access programs during ALS drug development. We believe that these should be reserved for treatments that have at least some independently verifiable safety data. In our opinion, that is not the case with GM604, so we feel that expanded access is premature at this time. When we can independently verify safety data, we hope to see a GM604 group expanded access program that has transparent entry criteria, systematic objective outcome measures, full disclosure of results, and, as suggested by the FDA, allows for a sponsor’s cost recovery but not for profit (39).‌‌‌

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Precision Stem Cell

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At ALSUntangled our goal is to provide guidance on the mechanism, pre-clinical data, anecdotal evidence, trials and risks of various alternative treatment options. Our goal is not to challenge the rights of PALS to pursue these options. Along these lines, MSC transplants in general have a promising mechanism, good pre-clinical data in ALS models and appear reasonably safe when performed with approved standardized protocols, proper oversight, and monitoring. However, the specific protocols used at PSC for PALS are poorly detailed, appear variable in terms of the sources of MSCs being used, the ways these are being modified and the places where these are being inserted, have no provision for confirming the material being inserted, and have only subjective and usually brief improvements associated with them. ALSUntangled strongly supports further study of MSC in PALS, but only with transparent, reproducible protocols that include confirmation of transplanted material and objective outcome measures. At this time, it does not appear to us that PSC is meeting these criteria.

Endotherapia

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Endotherapia has a proposed mechanism that hinges on the ability of an isolated laboratory’s immunoblots to identify the cause and specific pathways that are driving ALS progression. In our opinion this ability has never been convincingly demonstrated. While there is a flawed animal study supporting the utility of Endotherapia in rats, such studies rarely translate into useful human treatments (29). The data on Endotherapia in PALS have so many problems that we believe they are uninterpretable. ALSUntangled does not recommend the use of Endotherapia for ALS at this time. A reasonable next step would be a study to validate the utility of the above-described immunoblots, ideally by a group without a potential conflict of interest.

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Methylcobalamin

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MeCbl has promising mechanisms and positive preclinical data from two different ALS models. Unfortunately, the anecdotal data we found did not identify any clear specific benefit, and the best of three clinical trials was unable to show an overall difference in ALSFRS-R progression or survival between PALS treated with MeCbl and those treated with placebo (26). A sub-group of patients with very specific pretreatment progression rates of 1–3 ALSFRS-R points over 12 weeks, and very early disease (less than 12 months from symptom onset) may have had benefit (26). This finding needs to be replicated, especially since an earlier study suggested patients with longer disease duration were more likely to benefit (20). We would like to see a full traditional sub-group analysis (28) carried out on the data from the third trial (26). This sub-group analysis could then be used to design inclusion criteria for a new phase III trial comparing MeCbl 50 mg twice a week IM to placebo. The new trial could measure serum B12 and homocysteine, and have pre-planned sub-group analyses that are both logical and practical. While we wait for this, PALS who wish to try MeCbl are reminded that the above studies used very high, injected doses, which appear to be available only by prescription. Lower over-the-counter doses administered orally have not been studied. It is well established that over-the-counter oral supplements may be of poor and inconsistent quality (32). Some over-the-counter oral vitamin B supplements contain not only B12 but also B6, which in large quantities can be harmful to the nervous system (33).

Mito Q

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MitoQ has a promising mechanism, positive preclinical data from two different ALS models, and appears reasonably safe and inexpensive, especially at doses of 10 mg daily. Available anecdotal data are insufficient to determine how helpful this might be in PALS. A small open-label pilot trial with validated ALS diagnoses and outcomes appears warranted.

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Rife Machine and Retroviruses

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It is possible, although currently unsettled, that ALS in some individuals may be due to a retrovirus. Even if true, however, Rife’s microscope technology, his identification of specific frequencies for pathogens, and the ability of Rife radio frequency machines to kill pathogens, are all unproven and highly implausible. We have identified no verified cases of ALS improving on any objective outcome measure with the Rife Machine. At this time ALSUntangled does not support the use of the Rife Machine for ALS.