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 in bulbar physiology. However, its long-term effect on bulbar function is unclear, and one open-label study showed a lack of benefit in one year. There is no evidence suggesting Nuedexta slows down progression or prolongs survival. Nuedextacauses mild to moderate side effects, but severe side effects directly caused by Nuedexta have not been reported. It should be avoided in patients with a known history of prolonged QT interval. Given all this, we feel there is sufficient evidence to consider Nuedexta treatment for bulbar dysfunction in ALS patients with and without PBA. Financial burden and periodic assessment of its efficacy should be considered for the latter.
Pre-clinical models (animal or cell models recognized by ALSUntangled reviewers to be relevant to ALS)
There are theoretical mechanisms supporting the potential role of astaxanthin in the treatment of ALS, however, there are no ALS-specific pre-clinical data exploring this treatment. One verified“ALS reversal” occurred while taking astaxanthin in the setting of a cocktail of various other therapies—an association that does not prove causality. There have been no clinical trials of astaxanthin in PALS. Natural astaxanthin appears to be generally safe and inexpensive. We believe there is a need for further pre-clinical and/or clinical trials of natural astaxanthin in disease models and PALS, respectively, to further elucidate efficacy.
There is a theorized association between MAP and ALS, and two published case reports described improvements in ALS-like conditions (both with atypical features) after treatment with antimycobacterial antibiotics. Based on these, we believe it would be reasonable to perform chest imaging in PALS who have features of their history or exam that are atypical for ALS such as pain, fevers, or eye movement abnormalities. If the chest imaging is abnormal, more specific testing for mycobacteria may be indicated. Until there is more clear evidence of an association between MAP and ALS, we cannot endorse the widespread use of potentially toxic antimycobacterial antibiotics for PALS.
As an immunosuppressant drug, AZA has a plausible mechanism for slowing the progression of ALS. However, there is no pre-clinical data to support its use and two clinical trials did not support efficacy. There are 2 published cases in which
ALS reversals occurred on AZA, but it is not clear to us that the AZA actually contributed to the ALS improvements. One of these patients also had myasthenia gravis, which is known to cause reversible weakness and therefore complicates the measurement of ALS. The other patient was taking many different medications and supplements along with AZA. AZA has very serious, potentially fatal, both short and long-term risks associated with its use and requires medical monitoring. Based on the
available data, we do not advise the use of AZA as an ALS treatment
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.
Many ingredients contained within LEAP2BFIT could, at least in theory, be beneficial in ALS. Some of these ingredients have supporting animal or human studies. However, it is unknown if these ingredients are being provided in therapeutic quantities since the dosages are not disclosed. Furthermore, it is impossible to know the net positive or negative effect of so many ingredients without carefully testing the combination. Based on the above discussions, we do not currently recommend LEAP2BFIT as a way to slow, stop, or reverse ALS.
Vinpocetine has several plausible mechanisms by which it could slow ALS progression. There are two PALS online who reported improved motor functions on supplement cocktails containing Vinpocetine, but many other PALS have had no
benefits. Serious side effects from Vinpocetine are rare and it is inexpensive. We support further study of Vinpocetine in ALS, but our group was split on what the next step should be; some were in favor of a study in a pre-clinical ALS model and others were in favor of a small human trial to confirm its benefit on cramps (7) and to explore whether it is safe, tolerable and might slow disease progression.
It is unknown if fungi exist in the brain of PALS. If they do exist, it is unknown if they have any pathogenic effect, and unknown if antifungal drugs would modify ALS disease progression. There are no pre-clinical ALS model studies, verified ALS cases, or ALS clinical trials to suggest that antifungals would be of any significant benefit to PALS, and these medications can cause harm. At this time, we strongly discourage PALS from taking antifungal drugs for their ALS disease. We hope in the future that independent laboratories will look for fungi in the CNS of PALS using more appropriate experimental methods.
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