ALS Untangled™

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

Risks (harms that occurred on this treatment)

Butyrates

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Butyrates have plausible mechanisms for slowing ALS progression and positive pre-clinical studies. One trial suggests that sodium phenylbutyrate (NaPB) in combination with Tauroursodeoxycholic acid (TUDCA) can slow ALS progression and prolong survival, but the specific contribution of NaPB toward this effect is unclear. Butyrates appear reasonably safe for use in humans. Based on the above information, we support a trial of a butyrate in PALS, but we cannot yet recommend one as a treatment.

https://www.tandfonline.com/doi/pdf/10.1080/21678421.2022.2045323

Basis

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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

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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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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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Accilion

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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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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.

Gluten-Free Diet

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Theoretically, gluten-induced autoimmunity could trigger ALS. However, the data supporting this link are weak, consisting of two association studies and a single case-report. Further studies are needed to confirm the relationship between GRDs and ALS, and the utility of the GFD in patients with both conditions. In spite of the fact that GFD is reasonably safe, it is a complex undertaking and is more expensive than a standard diet. While we wait for better data, it would be reasonable to screen PALS who have GI symptoms, iron-deficiency anemia, or an abnormal brain MRI for the antibodies associated with GFDs. Those with elevated antibodies could be referred to a gastroenterologist for further work-up, and if this is consistent with a GRD, then GFD could be tried under the guidance and monitoring of a dietician.‌‌‌‌

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Protandim

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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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