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.
Patient trials
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’.
RT001
RT001 has a novel mechanism for reducing oxidative stress that could theoretically work better than more traditional antioxidants. In the small trial of patients with Friedreich’s ataxia, it seems to be safe and well-tolerated at lower dosages but can cause nausea and diarrhea at higher doses. At the time of this writing, there is very little efficacy or safety data in PALS. An expanded access program is underway which allows PALS at certain clinics to try this compound free of charge. Data resulting from this expanded access program will help the planning of a possible future clinical trial.
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Basis
Basis has mechanisms of action that could theoretically be useful in treating ALS. It appeared reasonably safe in a small, short duration study of healthy volunteers and it is fairly inexpensive. However, we found no data in preclinical ALS models, no case reports, and no trials in PALS. Based on this lack of data, ALSUntangled cannot currently recommend use of Basis to slow, stop, or reverse the progression of ALS.
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L-Serine
L-serine is a reasonably inexpensive, widely available nutritional supplement that has a plausible mech-anism by which it could help a subset of patients who might have ALS from BMAA-toxicity. A small Phase I trial showed that L-serine up to 15 g twice daily is relatively well tolerated. A larger follow up trial is planned and will shed further light on its safety and utility as an ALS therapeutic. Unfortunately, since it is challenging to reliably measure BMAA in PALS, it will be difficult to identify the subset most likely to respond. Until a reliable assay for measuring BMAA exposure in living people arises, or a follow up trial confirms safety and demonstrates benefit independent of this, we cannot recommend L-serine as a treatment for ALS.
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Endotherapia
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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Acupuncture
Acupuncture is reasonably safe, and has potential mechanisms of action, pre-clinical studies and case reports suggesting that it could be a useful treatment for ALS. However, before it can be endorsed even as a candidate for a phase II trial, the studies described above need to be independently replicated using more clearly verified diagnoses and more rigorous designs, including appropriate controls and validated ALS outcome measures.
Vitamin D
At this time, there is evidence that PALS, like those with other chronic illnesses, are at increased risk for vitamin D deficiency. It is, therefore, reasonable to screen PALS for this. If vitamin D deficiency is found, it seems reasonable to supplement vitamin D according to established guidelines (31) in order to avoid medical complications of vitamin D deficiency. It is not yet clear, however, that vitamin D supplementation can slow disease progression, improve muscle strength, or reduce falls in PALS. We support further studies to answer these questions.
Hyperimmune Goat Serum for ALS
The mechanism of Aimspro remains unproven; if it is an immunomodulator and/or a modulator of sodium channels, it theoretically could be useful in ALS. A single, detailed but significantly flawed case report documents slowing in decline of certain respiratory functions in a patient claiming to have ALS, who started Aimspro shortly after bipap. Based upon this limited information, ALSUntangled supports further study of Aimspro, either in ALS animal models or in a small phase 2 trial with clear and objective endpoints carried out by skilled trialists familiar with the problems inherent with ALS clinical studies. Until a trial is undertaken, however, we do not support further use of this product by PALS.