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
Patient trials
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.
Vitamin E
Vitamin E (a-tocopherol) is perhaps the most studied supplement in the history of ALS and was taken by one of the most famous ALS patients. Vitamin E has mechanistic potential in ALS as an antioxidant but appears in the SOD1 mutant mouse model to only have an effect on delaying disease onset. This bears out in human populations as large prospective cohorts show that long-duration vitamin E supplementation may decrease the risk of ALS, but randomized clinical trials show that even high dose vitamin E does not benefit the disease once ALS has been diagnosed. Although it is inexpensive and safe, we do not recommend vitamin E to slow, stop or reverse ALS
based on the lack of efficacy in clinical trials.
Glutathione
As an ALS treatment, glutathione and cysteine-containing supplements that increase glutathione appear reasonably safe, and they have a plausible mechanism, positive preclinical data and 2 interesting case reports. Unfortunately small clinical trials of glutathione itself and of acetylcysteine showed no significant benefit. Given these negative clinical trials, we do not advise PALS to take glutathione or cysteine-containing supplements for their ALS at this time.
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Penicillin G/Hydrocortisone
In our opinion, there is no convincing evidence that GABA overload plays a role in ALS progression. PNG/HC has other theoretical mechanisms by which it could slow ALS progression, but previous human trials involving steroids and a trial of a b lactam with more potent effects on glutamate did not help. We have not been able to confirm the diagnoses, nor the improvements described in the case series of 3 PALS taking PNG/HC; however, even if these treatment effects were real, these improvements were transient and quickly became unresponsive to treatment. Unless the ongoing placebo-controlled trial shows objective and sustained clinical improvements, we do not recommend that PALS take this expensive and risky combination of penicillin G and hydrocortisone.
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Antiretrovirals
Antiretrovirals are a group of diverse drugs developed for HIV infections that vary widely in theoretical efficacy against HERVs, side effect profiles, and cost. HERV expression is apparently increased in some PALS; however, it is unknown if this is a
beneficial, neutral, or pathological process. Furthermore, it is not clear if ARV-targeted mechanisms such as cell infection and viral replication are taking place in PALS. Based on the lack of evidence for use of ARVs in PALS who test negative for HIV and HTLV, we cannot recommend them as a treatment for ALS. We look forward to the results of the two ongoing trials of ARVs in PALS.
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Hyperbaric Oxygen
Although there are plausible mechanisms by which HBOT could work in ALS and a flawed pre-clinical study showing benefit in a mouse model, the best available human trial of HBOT showed no benefit. Given this negative human trial and the fact that HBOT has potentially serious complications, we do not recommend HBOT for patients with ALS at this time.
Kim Cherry’s ALS reversal, which occurred on HBOT and several other alternative treatments, appears very interesting. We do not think this is due to HBOT alone. There are other rare examples of ALS reversals on different (or sometimes no) treatments (28). Other explanations for these reversals include undetected ALS mimics syndromes or endogenous mechanisms that confer resistance to the disease (28). We look forward to further study of cases like this (29).
Declaration of interest: ALSUntangled is sponsored by the ALS Association and the Motor Neurone Disease Association.
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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.