Methylenblue inhibits Prions

I came across the alleged effectiveness of methylene blue against prions (Creutzfeldt-Jakob disease, Alzheimer’s disease, Parkinson’s disease, Long Covid, etc.) in a Substack post and researched this information.

Here are the source articles

• Molecular background of the neuroprotective effect of methylene blue
• Methylene blue completely inhibits prion polymerization

And – my research shows, to my astonishment:

yes, there are indeed scientific studies on PubMed that examine the effect of methylene blue on prions.

The bold claim that it “can prevent all types of prions” is exaggerated.

What we have: strong in vitro evidence that methylene blue (MB) can completely inhibit the replication of true prions (PrPSc) in a PMCA model of humans (vCJD), cattle (BSE), cervids (CWD), and mice, among others.

This has not yet been demonstrated in vivo or clinically. There is also early negative data in cell culture. At the same time, there are many studies in which MB or LMTM/LMTX influences prion-like proteinopathies (Tau, alpha-synuclein, Aβ, TDP-43). (MDPI, PubMed)

In any case, several studies show promising results that methylene blue can inhibit the oligomerization, fibrillization, and replication of prion proteins (PrP). I summarize the most relevant studies based on PubMed searches:

• A 2024 study tested various compounds for their anti-prionic activity using the protein misfolding cyclic amplification (PMCA) method. Here, methylene blue was able to completely inhibit prion replication in all tested species (mouse, cattle, deer, and humans, including variants such as vCJD). The IC50 value (concentration for 50% inhibition) was 7.7 μM for human vCJD prions. This suggests broad efficacy, but this is an in vitro screening. Creutzfeld-Jakob Study 2024
• In an earlier study from 2012, the binding of methylene blue to prion proteins (from humans, sheep, and mice) was investigated. It inhibited oligomerization by approximately 30% (pH-dependent) and completely suppressed the formation of amyloid fibrils at a molar ratio of 1:2 (PrP:MB). Binding occurs at a surface cleft of the protein, disrupting the aggregation pathway. Here, too, in vitro.
• Another study from 2020 looked at tau proteins that have prion-like properties (e.g., in Alzheimer’s-like tauopathies). In a mouse model, methylene blue reduced the amount of soluble tau oligomers in the brain, thus preventing cognitive impairment. Tau oligomers act in a prion-like manner as “seeds” for aggregation. This is relevant for “prion-like” proteins, but not for classic PrP prions.

Other studies mention methylene blue in the context of prion filters for blood products or general neurodegenerative diseases, but not for direct prevention of all prion types. There is evidence of potential therapeutic applications, but clinical trials in humans are largely lacking, and side effects (e.g., at high doses) must be considered.

True Prions (PrPSc) – Studies and Reviews

• Pritzkow 2024 (Biomolecules): PMCA screen with, among others, vCJD, BSE, CWD, and mice. Only methylene blue blocked prion replication in all tested species; IC50 for vCJD ~7.7 µM. In vitro. (MDPI, PMC)
• Cavaliere 2013 (BBA Mol Basis Dis): MB binds to a surface furrow of PrP and inhibits oligomerization/fibrillization (human/ovine/murine PrP; pH-dependent). In vitro. (PubMed)
• Korth et al. 2001 (PNAS): Tricyclics against prions in infected cells; MB itself did not inhibit PrP Sc formation and was >500 nM cytotoxic. Cell culture, negative for MB. (PubMed, PMC)
• Shim 2022 (Review, Prion therapeutics): Overview; MB discussed as a PrPC binder and aggregation modulator; no clinical evidence for prion diseases. (PMC)
• Barreca 2018 (Review, Pharmacological Agents targeting PrPC): summarizes MB binding to PrPC and anti-aggregative effects; Preclinical data. (MDPI)
• Sobek 2024 (Methods, binding sites on PrP): Methodical characterization of multiple binding sites of small molecules to PrP; MB as a reference among the tested substances. Mechanistic context. (PMC)

Prion-like Proteinopathies – Methylthioninium/Methylene Blue and Derivatives

• Tau, Cellular models (Harrington 2015, Sci Rep): LMTX/LMTM (reduced MB form) blocks prion-like tau aggregation in cellular systems; addresses limitations of methylthioninium chloride. (PMC)
• Tau, Mechanisms (Congdon 2012, PNAS/PMC): MB modulates Hsp70/proteasome, reduces tau aggregate load; in vitro/in vivo-close models. (PMC)
• Tau, mouse preventive (Hochgraefe 2015, Acta Neuropathol Commun): Preventive MB administration preserves cognition in tau transgenics; therapeutically late no benefit. (PMC)
• Tau, prion-like processing (Wischik 2018, Brain Sci/PMC): Methylthioninium reduces tau pathology and cognitive deficits in a preclinical model; prion-like processes discussed. (PMC)
• Tau, clinical LMTM data (Wilcock 2018, J Alzheimers Dis): Post-hoc/monotherapy analyses suggest possible effect in mild AD; randomized confirmation pending. (PubMed)
• Tau, Phase III re-analysis (Schelter 2019, J Alzheimers Dis): Concentration dependence hydromethylthionine; no differences in the original phase III primaries, but pharmacodynamic signals. (PMC)
• Tau, functional (Berrocal 2019, Int J Mol Sci): MB lifts tau-related PMCA inhibition on(human brain tissue, pig, cell models). (MDPI)
• Tau, negative result (van Bebber 2010, Neurobiol Dis): MB does not inhibit Tau/polyQ in a cell test; Example for model-dependent discrepancies. (ScienceDirect)
• Alpha-synuclein (Schwab 2018, Sci Rep/PMC): LMTM inhibits Alpha-synuclein aggregation; indication of possible relevance to synucleinopathy. (PMC)Aβ, photoactivated (Lee 2017, Sci Rep): Light-activated MB disassembles Aβ42 aggregates and reduces cytotoxicity; photodynamic option. (Nature)
• Aβ, 3xTg-AD mouse (Medina 2011, Neurobiol Aging/PMC): Chronic MB administration reduces soluble Aβ and improves early cognition. (PMC)
• Clinical/neuroprotection general (Tucker 2018, Transl Neurodegener): Review on MB and mitochondria; neuroprotective plausibility, no prion clinical efficacy. (PubMed)
• TDP-43, cell models (Yamashita 2009, FEBS Lett): MB reduces TDP-43 aggregates by approximately 50%; in combination with Dimebon. (PubMed)
• TDP-43/FUS, C. elegans & Zebrafish (Vaccaro 2012, Hum Mol Genet/PMC): MB rescues TDP-43/FUS-associated neurotoxicity; in vivo model organisms. (PMC)
• ALS models, negative (Audet 2012, Neuroscience): MB failed in SOD1(G93A) mice and TDP-43(G348C) mice; no functional benefits. (Methylene blue administration fails to confer… href=”https://pubmed.ncbi.nlm.nih.gov/22230045/?utm_source=chatgpt.com”>PubMed)

Practical Application

• Strongest prion-specific evidence: the 2024 PMCA study with MB (broad across the species spectrum, but only in vitro). Clinical studies on CJD/BSE/CWD with MB are lacking. Early cell culture data are partly negative. (MDPI  PubMed)
• Prion-like proteinopathies: Numerous positive preclinical signals (Tau, alpha-Syn, TDP-43), heterogeneous results and limited/inconsistent clinical data (LMTM/LMTX). (PMC, PubMed)

Conclusion: The statement that MB prevents all types of prions is exaggerated. An antiaggregative/antipronic effect of MB in certain in vitro systems and in prion-like aggregates is plausible and proven. Translationally, it remains open whether and how this can be translated in vivo in humans.

Methylenblue for Brain Metabolism

About The author of the article, Dr. Sabine Stebel

Via Twitter, I came across a Substack entry by a truly nasty conspiracy theorist, “Dr. Sabine Stebel,” who mercilessly spreads officially recognized information about various incidents in the US in German, even though everything is rightly suppressed in German-speaking media!

Apparently, she is not a doctor, otherwise she would already be unemployed or exiled abroad for this reckless dissemination of theories (supposedly proven) in the US. Dr. Stebel, apparently a physicist, materials scientist, or chemist, Sabine has the nerve to make statements on such serious topics as prions.

She even quotes from Russian studies from Moscow, which clearly violates every scientific code of ethics and thus deepens distrust in the German state’s ability to clean itself up. The important EU Service Act, which should a priori prevent such messages on social media, also appears to be permeable.