Because components of the Wahls diet may affectinflammation, oxidative stress and mitochondrialdysfunction, it has plausible mechanisms for slow-ing ALS. Although a cross-sectional study suggeststhe intake of certain macro- and micronutrientsenriched in the Wahls diet was associated with bet-ter baseline motor function and lower risk for get-ting ALS, no case reports or clinical trials areshowing the Wahls diet affects disease progressionor survival in PALS. On the contrary, the clinicaltrial in MS patients showing significant weight lossand essential vitamin and mineral deficienciesraises serious concerns; two thirds of PALS alreadyexperience weight loss at the time of diagnosis,and weight loss is a strong predictive factor for fastdisease progression and shorter survival.Therefore, we cannot endorse the Wahls protocolfor slowing ALS progression.
Pre-clinical models (animal or cell models recognized by ALSUntangled reviewers to be relevant to ALS)
PoNS Device
Considering the fact that electrical stimulation was first used as a medical treatment more than 100 years ago (30), and first used as an ALS treatment 30 years ago (31), it is disappointing that we have yet to find a clear way to use this to help PALS. PoNS™ is a newer version of this. There is a vague theoretical mechanism (neuromodulation) by which PoNS™ could potentially modulate neuroplasticity in the brainstem and cortex, but whether it provides any beneficial or deleterious effects on ALS progression is currently unknown. While there are early, promising data showing that the PoNS™ device improving gait in patients with multiple sclerosis, this may not translate to PALS. There are no pre-clinical data or clinical trials of PoNS™ therapy in PALS to determine efficacy. The PoNS™ device appears to be relatively safe but its substantial cost and prescription-only status will limit accessibility for PALS. Given the current lack of ALS-relevant data, we cannot currently support the use of PoNS™ therapy to slow, stop, or reverse ALS progression. We hope that this review of PoNS™ and the broader topic of neurostimulation spurs future research toward helping PALS.
Lions Mane
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 ALS. We hope to see the validation of its neuroprotective and anti-inflammatory benefits in ALS disease models, which may ultimately lead to clinical trials in PALS.
Nuedexta
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.
Astaxanthin
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.
Anti-Mycobacterial Antibiotics
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.
Azathioprine
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
Proprionyl-L-Carnitine
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.