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ALS Untangled™

ALSUntangled™ reviews alternative and off label treatments (AOTs), with the goal of helping people with ALS make more informed decisions about them.

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Fecal Transplants

Updated Review
Published: July 18, 2022
Since our last update, we found a new case report published in a peer reviewed journal (J Biomed Res. 2022 Jun 28:1-8. doi: 10.7555/JBR.36.20220088. Online ahead of print). This described a person with ALS who received a series of fecal transplants and then had their ALS progression improve. The authors nicely describe the limitations of associations like this, especially given the known variability in ALS progression in individuals over time. Although it has to be interpreted with caution, this published case warrants a change in our TOE "Cases" grade to A. We look forward to the results of an ongoing trial of this therapy in people with ALS (https://clinicaltrials.gov/ct2/show/NCT03766321?term=fecal&cond=ALS&draw=2&rank=1).
Updated Review
Published: December 21, 2020
Since our initial review we found 3 new relevant preclinical studies (Amyotrophic Lateral Scler Frontotemporal Degen 2017;18:245–6; Nature 2019;572:474-480; Nature 2020;582:89-94). These suggest plausible mechanisms by which fecal transplants could slow ALS progression, including modulating neuroinflammation and neuroprotection. As a result, we change our TOE “Mechanisms” grade from D to B. These show that in 3 different ALS animal models, changing the gut microbiome favorably slows disease progression. As a result, we change our TOE “Pre-Clinical” grade from U to B. We found no new case reports, trials, or risks to warrant grade changes in those TOE categories. These new studies warrant a change in our conclusion as well. Fecal transplants (and other ways to change the gut microbiome) now appear to be more promising. We are glad to see ongoing efforts to define “good” and “bad” microbiomes in patients with ALS, and trials to try and change microbiomes to slow, stop or reverse progression (NCT04499963, NCT03766321).

Key Information

Click on any letter grade below for more info:
Mechanism Grade: B
Preclinical Trials Grade: B
Cases Grade: A
Trials Grade: U
Risks Grade: B
Published: Jul 2013
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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.

Mechanistic plausibility

Grade A: Shown in a peer-reviewed publication to act on a relevant mechanism in humans

Mechanistic plausibility

Grade B: Shown in a peer-reviewed publication to act on a relevant mechanism in pre-clinical model(s)

Mechanistic plausibility - C

Grade C: Theoretically and plausibly acts on an ALS-relevant mechanism in humans

Mechanistic plausibility

Grade D: Acts on a biological mechanism but it is not clear that this mechanism is relevant in ALS

Mechanistic plausibility

Grade F: Implausible; would violate known principles or laws of biology

Mechanistic plausibility

Grade U: No useful information was found for this category

Pre-clinical models (animal or cell models recognized by ALSUntangled reviewers to be relevant to ALS)

Grade A: Two or more peer-reviewed publications reporting benefits in well-designed studies.

Animal studies are assumed to be ‘well designed’ when they follow published guidelines. When they deviate from these they are considered ‘flawed’.

Pre-clinical models (animal or cell models recognized by ALSUntangled reviewers to be relevant to ALS)

Grade B: One peer-reviewed publication reporting benefits in a well-designed study.

Animal studies are assumed to be ‘well designed’ when they follow published guidelines. When they deviate from these they are considered ‘flawed’.

Pre-clinical models (animal or cell models recognized by ALSUntangled reviewers to be relevant to ALS)

Grade C: One or more peer-reviewed publication(s) reporting benefits in flawed studies.

Animal studies are assumed to be ‘well designed’ when they follow published guidelines. When they deviate from these they are considered ‘flawed’.

Pre-clinical models (animal or cell models recognized by ALSUntangled reviewers to be relevant to ALS)

Grade D: One or more non-peer reviewed studies reporting benefits (published on a website or in an abstract)

Pre-clinical models (animal or cell models recognized by ALSUntangled reviewers to be relevant to ALS)

Grade F: The only studies available show no benefit

Pre-clinical models (animal or cell models recognized by ALSUntangled reviewers to be relevant to ALS)

Grade U: No useful information was found for this category

Patient case reports

Grade A: One or more peer-reviewed publications reporting benefits with validated diagnosis and benefits

Patient case reports

Grade B: More than one unpublished report of benefit with validated diagnosis and benefits

Patient case reports

Grade C: One unpublished report of benefit with validated diagnosis and benefits

Patient case reports

Grade D: Subjective report(s) of benefit without validated diagnoses and/or benefits

Patient case reports

Grade F: The only reports available show no benefit

Patient case reports

Grade U: No useful information was found for this category

Patient trials

Two or more peer-reviewed publications describing benefits in well-designed randomized, blinded placebo-controlled phase III trials

Patient trials

Grade C: One or more peer-reviewed publications reporting benefits in a well-designed randomized, blinded, placebo-controlled phase I or II trial

Patient trials

Grade D: One or more peer-reviewed publications reporting benefits in a flawed trial.

Flawed trials means those in which there are identifiable problems with patient selection, randomization, blinding, controls or follow-up. These have ‘high or unclear risk of bias’ according to published criteria. Well-designed trials are those that have ‘low risk of bias’.

Patient trials

Grade F: The only trials available show no benefit

Patient trials

Grade U: No useful information was found for this category

Risks (harms that occurred on this treatment)

Grade A: No exposed patients appear to have experienced harms

Risks (harms that occurred on this treatment)

Grade B: More than 0% but less than 10% of exposed patients experienced harms (no hospitalizations or deaths)

Risks (harms that occurred on this treatment)

Grade B (oral): More than 0% but less than10% of exposed patients experienced harms (no hospitalizations or deaths)

Grade D (intravenous): More than 0% but less than 5% of exposed patients experienced death or hospitalizations

Risks (harms that occurred on this treatment)

Grade C: At least 10% of exposed patients experienced harms (no hospitalizations or deaths)

Risks (harms that occurred on this treatment)

Grade D: More than 0% but less than 5% of exposed patients experienced death or hospitalizations

Risks (harms that occurred on this treatment)

Grade D: More than 0% but less than 5% of exposed patients experienced death or hospitalizations

Grade F: At least 5% of exposed patients experienced death or hospitalization

Risks (harms that occurred on this treatment)

Grade F: At least 5% of exposed patients experienced death or hospitalization

Risks (harms that occurred on this treatment)

Grade U: No useful information was found for this category

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