The monograph “When ALS Is Lyme” is filled with errors in logic, misinterpretations of scientific papers, controversial statements that are either not referenced or refer to unverifiable anecdotes, and omissions of data contradicting its authors’ opinions. It fails in its attempt to argue that there is a connection between ALS and Lyme disease. At this time ALSUntangled does not recommend Lyme testing for patients with classical ALS. We sincerely hope that the Vaughters’ unqualified medical advice, baseless conspiracy theories and accusations do not alienate PALS from mainstream specialized multidisciplinary ALS clinics. Within these clinics appropriate patients with atypical motor neuron diseases (pure lower, pure upper, accompanied by rash, headache, stiff neck, photosensitivity, fever, reversible facial nerve palsy, eye movement abnormalities, dermatomal pain and sensory loss), especially those coming from Lyme-endemic areas, will be tested for Lyme according to CDC criteria, and also treated rationally according to validated guidelines if Lyme is diagnosed. More importantly for the vast majority, those who come to specialized ALS clinics will receive competent and caring healthcare teams that will work to optimize the length and quality of their lives, and facilitate their participation in research toward a cure.
Patient case reports
Coconut oil has plausible mechanisms for use in ALS involving raising ketone bodies and lipid levels. Ketogenic and high fat diets may have helped slow motor neuron loss in small ALS animal studies with many flaws. Two online PALS have reported subjective improvements in muscle strength while taking coconut oil, while four others have not. One of these two is anonymous and described on a website promoting a book about coconut oil, and the other apparently has a very atypical slowly progressive form of ALS and takes at least one other supplement. Coconut oil at doses of 1–4 tablespoons per day appears generally well tolerated but it is not entirely clear how well these doses raise blood ketone levels. Although several large respected groups have warned against coconut oil intake in large amounts, the rationale behind these warnings has recently been called into question. Given all this, ALSUn- tangled supports further careful study of coconut oil or other methods of raising ketone bodies in patients with ALS. A reasonable next step would be a small case series of well-characterized PALS using coconut oil or other methods to raise blood ketone levels into the range found to be effective in epilepsy and possibly Alzheimer ‘ s, compared to a well-matched historical control group on objectively verifiable outcome measures.
Disclosures: ALSUntangled is sponsored by the Packard Center and the Motor Neurone Disease Association. 330 The ALSUntangled Group
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In our opinion, BV has biological effects that could potentially be useful in ALS. Two ALS-animal studies in which BV was injected into an unusual anatomic location showed positive effects on motor preservation and inflammatory markers; one showed improved survival. However, there are some significant problems with these animal studies. They do not meet methodological standards for preclinical animal research (14, 15) for the following reasons: treatment allocation was not randomized, power arguments are not presented, sample sizes are too small, potential confounders such as gender and copy number variation are not adequately addressed, criteria for determining symptomatic disease onset are not defined, blinding is not described, outcome measures in control animals are not compared to those in other studies to demonstrate external validity, and replication of results is via the same, rather than an independent group of authors. Furthermore, it is not currently possible to replicate pre-symptomatic drug delivery in humans with sporadic ALS. Many other compounds given pre-symptomatically to ALS-animals have failed to yield any positive benefit in human patients (16); indeed one immune-modulator that worked in ALS-animals actually appeared to accelerate disease progression in patients with sporadic ALS (17). It may not be possible to replicate the dosage of BV that was used in future human studies; by one estimate, for a 70g human this would require 70,000 bee stings twice a week (18). Finally and most importantly, we found very little data of any kind on BV exposure in humans with ALS; the two anecdotal reports describe unverified, non-overlapping benefits. Given all this, and the costs and risks of BV (which include death), ALSUntangled does not support the use of BV by patients with ALS outside of a study at this time. Replication of the animal studies via an independent group following published methodological guidelines and using a dosing regimen that could eventually be translated to human studies would be a reasonable next step.
In summary, luteolin is an interesting naturally occurring bioflavinoid that has been shown to have a myriad of functions in various models that could potentially be useful in slowing progression in patients with ALS. However, convincing data to support any positive effect on human ALS do not yet exist. Furthermore, there are legitimate reasons to be concerned about safety in patients with ALS including the need for a concomitant carbohydrate-deficient diet which might induce unwanted weight loss, and an anecdotal report of accelerated progression on this supplement. Until carefully controlled, well-designed human efficacy and safety studies are performed, ALSUntangled does not support the use of luteolin or any luteolin-containing products in patients with ALS.
Additional pharmacologic studies of LDN are needed to clarify its mechanisms of action. Some of its proposed mechanisms such as immunomodulation and neuroprotection could potentially be useful in ALS. However, there are no convincing data thus far to suggest that this is the case, and some limited data even raise a theoretical potential for a harmful effect. The benefits reported by a small Patients Like Me cohort are not consistent across participants, nor are they objectively verifiable. A small pilot study of a drug with similar mechanisms found no objective benefits in patients with ALS. Although reported costs are not exorbitant, there are reported and potential side-effects including liver toxicity. ALSUntangled does not recommend LDN use by patients with ALS at this time.
The mechanism of Aimspro remains unproven; if it is an immunomodulator and/or a modulator of sodium channels, it theoretically could be useful in ALS. A single, detailed but significantly flawed case report documents slowing in decline of certain respiratory functions in a patient claiming to have ALS, who started Aimspro shortly after bipap. Based upon this limited information, ALSUntangled supports further study of Aimspro, either in ALS animal models or in a small phase 2 trial with clear and objective endpoints carried out by skilled trialists familiar with the problems inherent with ALS clinical studies. Until a trial is undertaken, however, we do not support further use of this product by PALS.
In our opinion, there are many serious problems with MM’s approach. First, ALSUntangled is aware of no evidence to support MM’s theory on ALS pathogenesis. No case of ALS has ever been shown to be caused or exacerbated by emotional repression. Statements that patients may have somehow caused their own ALS by repressing their emotions are not only completely unfounded but potentially hurtful, as pointed out by the numerous angry patient and caregiver posts cited. MM’s statement that ALS development “is never really about genes” demonstrates that he has a shocking lack of awareness of more than a decade of ALS scientific literature. Despite his claim that he is not offering a treatment, rather merely “teaching or coaching”, it is clear that some of those he contacts see his program as a potential therapy. It is also clear that MM has implied to clients that his method can lead to dramatically effective results, potentially ‘solving’ their ALS problem. Reticence to call an intervention a ‘treatment’ is a strategy sometimes used to avoid laws that restrict the practice of medicine without a license. In our opinion, degrees in political science, economics, and finance are not qualifications to provide medical advice, medical teaching or medical treatment. In the future, we hope that MM will clarify his lack of medical training, and the fact that he is offering ‘teaching or coaching’ and not medical treatment, to prospective clients. We find no evidence that MM has ever ‘solved’ or cured ALS. Of his few reported ‘successes’ the two we could contact reported improved attitudes and motivations. It is not clear whether these had anything to do with his approach, or to one of the other alternative or off-label approaches being utilized, or (most likely) to the benign natural history of their unusual motor neuron diseases. We could confirm no definite motor improvements and Case 2’s neurologist documented worsened motor function over the past year. Thus, terms like ‘solved’ and ‘cured’ should not be used by MM in describing his offering to patients. Finally, MM’s practice of cold-calling patients with ALS and their families is morally and ethically questionable and is clearly disturbing to many. Patients and families who receive harassing phone calls should be aware that they can take action against the caller (5).
While we applaud the use of informed consent for portions of the XCell-Center protocol, and the presentation of pilot efﬁcacy and safety data, in our opinion many worrisome questions and problems remain. From a rational standpoint, we feel it is unlikely that all the diverse diseases (some without a name at all) being treated at the XCell-Center would respond to the same type of treatment. Nothing useful can be concluded from the ﬂawed ALS pilot data that are presented; the positive effects reported are very likely nothing more than a placebo effect as seen in the ﬁrst of our patients above. Regardless of whether the XCell product results in new motor neurons or promotes sprouting of existing ones, patients with ALS would not be expected to have improved motor function just one or even a few months after treatment as is being claimed. In our opinion, these misleading pilot data should be removed from the website or at least qualiﬁed with appropriate disclaimers.
We hope the XCell group will present all their ALS data for peer review, including evidence that their cells are surviving, as well as objective clinical outcome measures over a reasonable length of follow-up. This would be a useful ﬁrst step toward planning what is ultimately necessary to demonstrate the safety and efﬁcacy of this protocol – a randomized, blinded, controlled trial. Until this is completed, we do not condone the XCell Center’s protocol for patients with ALS.
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