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.
Risks (harms that occurred on this treatment)
At this time, there is evidence that PALS, like those with other chronic illnesses, are at increased risk for vitamin D deficiency. It is, therefore, reasonable to screen PALS for this. If vitamin D deficiency is found, it seems reasonable to supplement vitamin D according to established guidelines (31) in order to avoid medical complications of vitamin D deficiency. It is not yet clear, however, that vitamin D supplementation can slow disease progression, improve muscle strength, or reduce falls in PALS. We support further studies to answer these questions.
It is possible, although currently unsettled, that ALS in some individuals may be due to a retrovirus. Even if true, however, Rife’s microscope technology, his identification of specific frequencies for pathogens, and the ability of Rife radio frequency machines to kill pathogens, are all unproven and highly implausible. We have identified no verified cases of ALS improving on any objective outcome measure with the Rife Machine. At this time ALSUntangled does not support the use of the Rife Machine for ALS.
There is rapidly expanding evidence implicating alterations in the fecal microbiome in wide-ranging human diseases, including potential contributions via a gut-brain signaling axis in neurodegenerative and neuroimmunologic disorders. Proposed mechanisms such as immune modulation and the production of neurotoxins by clostridia or other microbiota could bypass an intact blood-brain barrier. To date, there are no data directly implicating the fecal microbiome in ALS, nor published case reports of FMT being tried in PALS. Data in other neurodegenerative and neuroimmunologic disorders are largely circumstantial, comprising a handful of published case reports. Therefore, ALSUntangled does not recommend FMT as a treatment for ALS at this time. However, it is plausible that the fecal microbiome plays a role in some neurologic disorders, including ALS. Given the lack of effective therapies and the relatively low cost and low risk of FMT – if performed by experienced clinical centers we support further investigations in this developing field. A reasonable next step would be a detailed molecular analysis of gut bacteria in ALS patients; certainly, these are the types of studies being advocated by the NIH Human Microbiome Project. If alterations are detected in the gut microbiome of ALS patients, a following step would be properly controlled studies in animal models, such as ALS mice. These studies could employ the same germ-free, and/or probiotic treatment regimens published in mouse models of EAE, Alzheimer’s disease, and obesity.
Mitochondrial dysfunction, glutamate excitotoxicity, and oxidative stress have all been implicated in ALS pathogenesis, and targeting these mechanisms individually or by a cocktail such as the Deanna Protocol could play a role in future ALS therapies. However, many of the preclinical and animal studies related to these pathways have not translated into successful treatments in patients with ALS. While there are anecdotal reports of improvements in patients with ALS on the Deanna Protocol, there is no convincing objective evidence of benefit yet. Thus, at this time, ALSUntangled does not recommend the Deanna Protocol to patients with ALS.
Before it can be recommended, a reproducible version of the Deanna Protocol should be shown to influence plausible physiologic mechanisms such as central nervous system ketone bodies, as well as clinically meaningful outcome measures such as ALSFRS-R and FVC in patients with ALS.
The NP001 formulation of sodium chlorite acts through a plausible mechanism and preliminary data suggest that it is safe and may slow ALS progression in some PALS. The WF10 formulation of SC appears to act through this same mechanism. Although WF10 is available for off-label use, it is very expensive, may have more side-effects than NP001, and at this time has only scant anecdotal evidence for efficacy in PALS. ALSUntangled supports further carefully monitored studies of NP001 and WF10 in PALS. In contrast, oral sodium chlorite has potentially dangerous and toxic side-effects may hasten disease progression, and is not clearly absorbed from the gut. We do not recommend further use of oral sodium chlorite unless it can at least be shown to be safe and to act on mechanisms in humans that are relevant to ALS.
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.
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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