A noninflammatory mRNA vaccine for treatment of experimental autoimmune encephalomyelitis, 2021, Krienke et al.

Mij

Mij

Senior Member (Voting Rights)
Abstract
The ability to control autoreactive T cells without inducing systemic immune suppression is the major goal for treatment of autoimmune diseases. The key challenge is the safe and efficient delivery of pharmaceutically well-defined antigens in a noninflammatory context. Here, we show that systemic delivery of nanoparticle-formulated 1 methylpseudouridine-modified messenger RNA (m1Ψ mRNA) coding for disease-related autoantigens results in antigen presentation on splenic CD11c+antigen-presenting cells in the absence of costimulatory signals. In several mouse models of multiple sclerosis, the disease is suppressed by treatment with such m1Ψ mRNA. The treatment effect is associated with a reduction of effector T cells and the development of regulatory T cell (Treg cell) populations. Notably, these Treg cells execute strong bystander immunosuppression and thus improve disease induced by cognate and noncognate autoantigens.
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Researchers have designed an mRNA vaccine that delayed the onset of and reduced the severity of multiple sclerosis-like disease in mice.

The vaccine restores the body’s tolerance to its own proteins, suppressing the disease's immune over reactivity.


https://science.sciencemag.org/content/371/6525/145/tab-e-letters
 
Really interesting paper, and first time I’ve heard of this novel “nanoparticle-formulated 1 methylpseudouridine-modified messenger RNA (m1Ψ mRNA) coding for disease-related autoantigens” technology. In many ways I feel a new treatment tech, like this one, will be the breakthrough for us. Thanks @Mij !
 
Mij said:
@leokitten

These are the researchers and research that is going to inadvertently figure out ME.
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My only concern with this particular tech is that, unlike MS, we don’t know of any consistent set of autoantigens present in a significant ME subset. Research has found for some limited subsets wrt to POTS or other comorbidities, but still haven’t connected it well to root ME pathophysiology if I’m remembering correctly.

But, as @Jonathan Edwards has suggested, if ME is a different kind of autoimmunity, primarily dysfunctional T cell activation in a hidden compartment like psoriasis and ankylosing spondylitis, we have to figure out what pro-inflammatory cytokines or chemokines (or other signals) might be causing this T cell activation. Maybe even a new monoclonal antibody (biologic) targeting these signals will work here, which is a mature technology and easier to develop.
 
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Interesting blog article on this paper and other uses of this technology, variations of which are potentially relevant in future if research discovers ME is due to chronic immune activation and what are some of the targetable pathways to bring back tolerance without suppressing the immune system.

Science Trans Med: More Things to Do With mRNA

 
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