In conclusion, corticosteroids are a class of medications with wide-ranging clinical uses and wellstudied effects on the immune system. ALS progression is associated with changes in immune system function, with the early disease states associated with anti-inflammatory immune markers and the advanced disease states associated with
pro-inflammatory immune markers. Although treatment with corticosteroids may cause a transient change in some immune markers, both preclinical and clinical trials have failed to show any clinical benefit in ALS. Multiple individual PALS
have self-reported improvement in weakness with corticosteroid treatment, but these cases have unclear generalizability and are limited by an uncertain ALS diagnosis, limited clinical data during the disease course, and heterogeneity of glucocorticoid type and dose. Although affordable and widely available, corticosteroids can have numerous side effects, and their risks are greater for higher doses or prolonged treatment. Therefore, we cannot recommend corticosteroids at this time as a way to slow ALS progression. Further research into immune system modulation in ALS is ongoing at many research centers internationally.
Patient case reports
Vitamin C
Vitamin C is safe and inexpensive. As an antioxidant, it has a plausible mechanism for influencing the course of neurodegenerative diseases. Two flawed preclinical studies by the same group showed benefits in a mouse model of familial ALS. There are two case reports in which it was associated with improvement. However, there are multiple possible explanations for the improvement in these cases. It is not clear which if any dose of vitamin C might be beneficial for PALS; a small clinical trial using oral vitamin C at 2,000 mg daily was unable to demonstrate benefits in PALS. Based on this negative trial, we currently advise against using vitamin C to treat ALS.
Melatonin
Melatonin has plausible mechanisms, some positive (and some negative) pre-clinical data, and two case reports in which it was part of a cocktail of treatments associated with recovery of lost motor function. As we have stated previously, there are
multiple possible explanations for cases like these. There was also a very small, flawed retrospective study suggesting that PALS taking it progressed more slowly and lived longer than PALS were not taking it. Melatonin appears safe at high doses, but evidence is lacking for a proven benefit in slowing disease progression in ALS. Furthermore, an optimal dose and route of administration have not been established. Based on this data, a pilot trial of melatonin in PALS would be reasonable, but we cannot yet recommend it as an ALS treatment.
LEAP2BFIT
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.
Curcumin
Oral curcumin is safe, inexpensive, and has at least four potential mechanisms by which it might theoretically be useful in treating PALS. Flawed preclinical studies showed benefits of a curcumin chemical analog in a cell model of ALS, three PALS experienced validated motor improvements on regimens including curcumin (although there are several alternative explanations for these improvements) and there is one small pilot trial showing some benefit of curcumin in PALS. Based on the evidence presented in this review, some of us are planning a trial of Theracurmin at 90 mg twice daily in PALS.
Click here to download the complete review.
L-Serine
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 will shed further light on its safety and utility as an ALS therapeutic. Unfortunately, since it is challenging to reliably measure BMAA in PALS, it will be difficult to identify the subset most likely to respond. Until a reliable assay for measuring BMAA exposure in living people arises, or a follow up trial confirms safety and demonstrates benefit independent of this, we cannot recommend L-serine as a treatment for ALS.
Click here to download the complete review.
TUDCA
Ursodiol has interesting mechanisms of action, appears reasonably safe and well-tolerated, has anecdotal reports of benefit in 6/21 of patients who report taking it, and a form of it (Yoo’s solution) was associated with slightly slower ALS progression in one out of three outcome measures within a poorly designed study that did not account for large numbers of drop-outs. However, analyses of ursodiol data from the well-conducted randomized, double-blind ceftriaxone trial show that ursodiol 300 mg twice a day is no better than placebo at prolonging survival or slowing ALS progression. Based upon this review, ALSUntangled does not recommend off-label use of ursodiol as a treatment for ALS, at least at doses of 300 mg twice a day. Determining whether higher doses or different formulations are effective will require further well-designed studies.
Cannabis
Cannabis has biological properties including immunomodulation and effects on excitototoxicity that suggest it could be useful in ALS. Evidence from small, non-randomized, unblinded animal studies suggest that it could potentially slow ALS progression, and anecdotal reports suggest that it could ameliorate troubling ALS symptoms. Given all this, ALSUntangled supports further careful study of cannabis and cannabinoids, the active ingredients contained therein. Natural cannabis, as a single agent, provides advantages similar to a multiple drug trial given its numerous mechanisms of action. A possible next step would be a small case series of well-characterized PALS using cannabis at controlled dosages that could potentially be monitored by blood levels of cannabinoids, compared to matched controls, performed in a geographic area where it would be legal.