Updated November 9, 2020
We found a new study showing benefits in a preclinical model of stroke (PLoS One 2013;8:e79002). It is not clear that this model is relevant to ALS, so we did not change our Pre-Clinical grade. We found no new case reports or trials. Given 2 reports of serious side effects in PatientsLikeMe participants with MS, we changed our Risks grade from B to D. Our conclusion remains the same. At this time ALSUntangled does not recommend that patients with ALS take apoaequorin. Reasonable next steps would include a controlled study of apoaequorin in an ALS animal model and/or a small series of well-characterized patients with ALS using validated outcome measures and including serum and CSF pharmacokinetics.
Updated May 6, 2024
As of May 2024, we found no new information to warrant any TOE grade changes.
Updated July 25, 2022
As of 7/25/22, we found no new data to warrant any grade changes or changes to our conclusion.
Key Information
Click on any letter grade below for more info:
Preclinical Trials Grade:
U
Published: Oct 2012
There is a rationale by which the calcium binding protein apoaequorin could work to slow ALS progression. Unfortunately, at this time there is insufficient information available to determine whether it does. The one small case series referred to above utilized a cocktail of therapies and is further weakened by the loss of its standardized outcome measurements. Information from the manufacturer suggests that apoaequorin is reasonably safe and well tolerated but there is no independent, systematic confirmation of this; two PatientsLikeMe members reported serious adverse events while taking it and it is fairly expensive.
At this time ALSUntangled does not recommend that patients with ALS take apoaequorin. Reasonable next steps would include a controlled study of apoaequorin in an ALS animal model and/or a small series of well-characterized patients with ALS using validated outcome measures and including serum and CSF pharmacokinetics.
Grade A: Shown in a peer-reviewed publication to act on a relevant mechanism in humans
Grade B: Shown in a peer-reviewed publication to act on a relevant mechanism in pre-clinical model(s)
Grade C: Theoretically and plausibly acts on an ALS-relevant mechanism in humans
Grade D: Acts on a biological mechanism but it is not clear that this mechanism is relevant in ALS
Grade F: Implausible; would violate known principles or laws of biology
Grade U: No useful information was found for this category
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’.
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’.
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’.
Grade D: One or more non-peer reviewed studies reporting benefits (published on a website or in an abstract)
Grade F: The only studies available show no benefit
Grade U: No useful information was found for this category
Grade A: One or more peer-reviewed publications reporting benefits with validated diagnosis and benefits
Grade B: More than one unpublished report of benefit with validated diagnosis and benefits
Grade C: One unpublished report of benefit with validated diagnosis and benefits
Grade D: Subjective report(s) of benefit without validated diagnoses and/or benefits
Grade F: The only reports available show no benefit
Grade U: No useful information was found for this category
Two or more peer-reviewed publications describing benefits in well-designed randomized, blinded placebo-controlled phase III trials
Grade C: One or more peer-reviewed publications reporting benefits in a well-designed randomized, blinded, placebo-controlled phase I or II trial
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’.
Grade F: The only trials available show no benefit
Grade U: No useful information was found for this category
Grade A: No exposed patients appear to have experienced harms
Grade B: More than 0% but less than 10% of exposed patients experienced harms (no hospitalizations or deaths)
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
Grade C: At least 10% of exposed patients experienced harms (no hospitalizations or deaths)
Grade D: More than 0% but less than 5% of exposed patients experienced death or hospitalizations
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
Grade F: At least 5% of exposed patients experienced death or hospitalization
Grade U: No useful information was found for this category
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