In conclusion, corticosteroids are a class of medications with wide-ranging clinical uses and wellstudied effects on the immune system. ALS progression is associated with changes in immune system function, with the early disease states associated with anti-inflammatory immune markers and the advanced disease states associated with
pro-inflammatory immune markers. Although treatment with corticosteroids may cause a transient change in some immune markers, both preclinical and clinical trials have failed to show any clinical benefit in ALS. Multiple individual PALS
have self-reported improvement in weakness with corticosteroid treatment, but these cases have unclear generalizability and are limited by an uncertain ALS diagnosis, limited clinical data during the disease course, and heterogeneity of glucocorticoid type and dose. Although affordable and widely available, corticosteroids can have numerous side effects, and their risks are greater for higher doses or prolonged treatment. Therefore, we cannot recommend corticosteroids at this time as a way to slow ALS progression. Further research into immune system modulation in ALS is ongoing at many research centers internationally.
Risks (harms that occurred on this treatment)
Butyrates
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
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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Inosine
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
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
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.