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 variable natural history of ALS progression. We conclude that WS is a reasonable compound for ALS trials, and we look forward to the results of the one trial that is underway.
Patient trials
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.
Insulin
Insulin treatment for ALS is an intriguing area for future research. However, the risks of insulin administration are significant and potentially lethal. Currently, there is no clinical evidence to support its use in PALS. Therefore, we cannot endorse insulin as a way to slow, stop, or reverse ALS progression at this time.
Caffeine
Caffeine is inexpensive, reasonably safe at doses of under 400 mg daily, and has plausible mechanisms by which it could slow ALS progression. However, data from pre-clinical models are contradictory and a two cohort studies showed no clear relationship between caffeine intake and ALS progression. Based on all this, we cannot endorse caffeine as anALS treatment.
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.
Ozone
Ozone therapy has possible mechanisms for treating ALS. A preclinical study in very small numbers of mTDP43 mice (which has yet to be peerreviewed) suggested benefits on motor function and survival (21,22); however, these benefits were not seen in mSOD1 mice (20). One verified “ALS reversal” occurred on a cocktail of alternative therapies including ozone (24); an association such as this does not prove causality. There have been no trials of ozone therapy in PALS. There may be potentially serious side effects associated with ozone therapy, depending on the dose (31). Based on all this, we support further investigation of ozone therapy in ALS cell or animal models, but we cannot yet recommend it as an ALS treatment.
Rituximab
ALSUntangled reviews alternative and off-label treatments on behalf of people with ALS who ask about them. Here we review rituximab, a drug which specifically depletes B lymphocytes. We show a current lack of evidence for a role of these cells in ALS progression. The one patient we found who described using Rituximab for their ALS found no benefit. Given all this, and the known serious risks of rituximab, we advise against its use as an ALS treatment.
You can read it here
https://www.tandfonline.com/doi/full/10.1080/21678421.2022.2122845?src=
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.