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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’.

Zinc 

March 17, 2025

Zinc has plausible mechanisms for modulating ALS progression, specifically with its roles in oxidative stress reduction and stabilization of SOD1 structure and function. Preclinical data has demonstrated potential benefits in slowing ALS progression at moderate doses in mouse models, but high doses without additional supplementation of copper were shown to be harmful. Clinical data on […]

Acetyl-L-Carnitine

July 30, 2020

There are good theoretical mechanisms for carnitines, some preclinical 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 […]

Resveratrol

April 4, 2019

Resveratrol is a dietary supplement that likely activates SIRT1 cellular pathways and may alter the gut microbiome. These are interesting mechanisms that may potentially alter the progression of ALS and do confer benefit in animal models of one type of familial ALS; however, to-date, there have been no trials of resveratrol in PALS. Some trials […]

RT001

January 28, 2019

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 […]

Antiretrovirals

April 25, 2018

Antiretrovirals are a group of diverse drugs developed for HIV infections that vary widely in theoretical efficacy against HERVs, side effect profiles, and cost. HERV expression is apparently increased in some PALS; however, it is unknown if this is abeneficial, neutral, or pathological process. Furthermore, it is not clear if ARV-targeted mechanisms such as cell […]

Basis

September 18, 2017

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 […]

L-Serine

November 29, 2016

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 […]

Endotherapia

January 25, 2016

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 […]

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