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Mechanistic plausibility

ISRIB

August 7, 2025

ISR over-activation may play an important role in ALS pathogenesis, as supported by data from pre-clinical models and PALS. Several different ISR inhibitors have been tried in ALS models or inPALS with mixed results; but given the differents pecific actions of these, it is not possible to generalize across the whole class. ISRIB can attenuate […]

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 […]

Ashwagandha

February 13, 2024

WS appears reasonably safe, has plausible mechanisms by which it might slow ALS progression, and has promising data obtained in multiple different clinical models of ALS. While there are also some interesting self reports from PALS and one verified ALS reversal on a compound containing WS, these must be interpreted with caution because of the […]

Lions Mane

January 2, 2024

While Lion’s Mane may have neuroprotective, neurotrophic, antioxidant, and anti inflammatory properties that could, at least in theory, potentially help ALS, there are still no studies in ALS relevant cell or animal models, nor in humans with ALS. Therefore, we do not have enough information to support the current use of Lion’s Mane for treating […]

Nuedexta

August 8, 2023

Nuedexta has plausible mechanisms for improving bulbar function in PALS. Some PALS reported concomitant improvement in bulbar function for at least a short period when taking Nuedexta for PBA. A well designed phase II trial in PALS demonstrated the efficacy of Nuedexta in patient-reported bulbar function, and the preliminary result of another trial showed improvement […]

Ketogenic Diets

October 21, 2021

Ketogenic diets have plausible mechanisms for treating ALS. One flawed preclinical study and two Patients Like Me participants reported benefits; these were not independently verified. Two other Patients Like Me participants and one patient underthe care of an ALSUntangled investigator did not show benefits. A trial of a ketogenic diet was only able to enroll […]

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 […]

Perampanel

February 20, 2019

Perampanel is a drug currently used to treat seizures which has a mechanism of action that theoretically could be useful in treating patients with ALS. A single flawed study in a mouse model of ALS showed some benefits of perampanel, but data from humans with ALS is quite limited. Due to the lack of data […]

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