Any new information on risks?

[William Stewart]

Hi Folks, it has been awhile since any update.  The last great summary I
am aware of is this one by Shin Jie Yong, based on the excellent
analysis of Kiang-Hua Goh and others:

https://medium.com/microbial-instincts/concerns-of-lipid-nanoparticle-carrying-mrna-vaccine-into-the-brain-what-to-make-of-it-42b1a98dae27

I repeat my belief in the proven value of vaccines to alleviate untold
human suffering across so many years.  However, I still have not seen a
case closing conclusion on the potential of these new mRNA vaccines to
pass the blood brain barrier.  Has anyone else seen any more resent
research or discussion or conclusions on this?

I also wonder if the now officially documented ability of the mRNA
vaccines to cause myocarditis influences the risk assessment that
significant LNP's may pass the BBB, or perhaps just gives us any
information to help judge the potential effects if it does so.  Can our
learned members render an opinion on whether this is relevant,
irrelevant, or somewhere in between?

https://www.bbc.com/news/world-asia-58380867

As an enormously unscientific sample of one, starting a week or so after
my Pfizer vaccination, I had quite significant heart arrhythmias for
several minutes several times a day for a couple weeks for the first
time in my life.  Canadian health care is free, but slow, and now that
they are gone for a couple months I am finally seeing a cardiologist on
16 Sep.  This is *NOT* proof of anything.  But it happened very
personally to me, and raises reasonable questions in my mind if the
documented ability to cause myocarditis gives any of the more learned
members of this list any useful information on the risk to the brain.

Cheers,
Bill

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[Shin jie Yong]

Hello everyone, 

It has indeed been a while. I looked through PubMed today, using the relevant search terms, and noted no noteworthy studies (as in experimental research) on this matter.

Two review papers that raised similar concerns, though, and I quote them here: 

• Igyártó et al. (2021): "Based on the current mRNA-LNP vaccine design, LNPs can be taken up by almost any cell type, near or far from the site of injection, transfecting them with the antigen-encoding mRNA [19]. Moreover, the mRNA used in these vaccines are nucleoside-modified to decrease inflammatory responses [13] and increase its stability in vivo, allowing extended periods of mRNA translation [20,21]. Also, a significant portion of the mRNA can be re-packaged and expelled from transfected cells in extracellular vesicles (EVs) [22••]. These vesicles could reach cells far from the injection site, further increasing the number of cells translating the antigen and extending the duration of its expression."
  
• Szabat-Iriaka and Le Borgne (2021): "Cationic lipid NPs (LNPs) are frequently used as drug delivery systems because they can enter cells more easily compared with anionic NCs. [40, 41] However, cationic LNPs are in general more toxic than anionic LNPs.[41] Positively charged LNPs are likely to increase brain vascular volume, to cause BBB damage, and potentially lead to the formation of cerebral edema.[42, 43] Some NMs, such as mRNA vaccines, contain optimized LNPs with an ionizable surface charge that is supposed to remain neutral at physiological pH.[44] However, it cannot be ruled out that this surface charge might change in individuals with conditions that can cause pH variations....Thus, toxicity risks resulting from NM interactions with the BBB are not negligible. Given the lack of specific methods for investigating the central toxicity of NMs, especially in vivo, it is important that the regulation provides a standardized methodological framework, which will help to better characterize the behavior of these NMs in different biological environments."
  

Therefore, it seems that this matter of LNPs and BBB remains unresolved at present. 

However, I wrote another article in July on the biodistribution of mRNA vaccine. Here's a friend link (but note that it automatically becomes the original link once the webpage loads).

In brief, the data thus far don't seem to suggest a cause for alarm. The off-targets of LNP-encapsulated mRNA vaccine appear minor, and even if this happens, the translated spike protein (if at all this happens too) won't bind to the ACE2 receptor. At least this means that vascular problems are unlikely to happen with the mRNA vaccine-encoded spike proteins, unlike SARS-CoV-2's one. 

But whether other immune reactions would occur to those off-targets (e.g., the brain or blood-brain barrier) or not, I'm not sure. Still, based on the latest safety data on mRNA vaccine that are published, there seem to be no major safety concerns besides myocarditis/pericarditis (and possibly ischaemic stroke). I have also written about this topic here (friend link), published just two days ago. 

Kind regards,

Shin

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[William Stewart]

Thanks Shin.  Your recent paper is a reassuring summary.  Those are large studies, with no evidence of cause for concern about near term effects.

I remain curious about the long-term effects, and especially the cumulative effect of multiple doses, since it seems possible we will need additional vaccinations against variants, possibly even annually as it evolves.  That is, as stated by Jacob Wes Ulm: "It also seems to indicate that the mRNA vaccines pose a much greater risk of systemic and critical tissue and organ damage than other vaccines, especially if multiple booster shots are needed, with side effects that may not manifest for years (with cumulative damage and chronic inflammation)":

https://groups.google.com/g/mrnadiscuss/c/bJ7ptHkch8A

Reports like the following (very small study) cause this non-medical scientist to wonder if this long-term cumulative effect is a cause for concern: "We report clinical and MRI features of seven individuals who received the Moderna (n = 3) or Pfizer (n = 4) SARS-CoV-2 mRNA vaccines. Within one to 21 days of either the first (n = 2) or second (n = 5) vaccine dose, these patients developed neurologic symptoms and MRI findings consistent with active CNS demyelination of the optic nerve, brain, and/or spinal cord":

https://pubmed.ncbi.nlm.nih.gov/34480607/

I wish there was definitive research available about the extent that the specific types of lipid nanoparticles used by each of the Moderna and Pfizer vaccines of passage pass the BBB.  That would seem to be the missing data on this issue.

Please all - keep any information or reasoning coming.

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-- 
William Stewart PhD, PMP
“Come now, and let us reason together.” - Isaiah 1:18
http://www.linkedin.com/in/billstewart
613-797-7744
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[Shin jie Yong]

Hello Dr. Stewart and others, 

The case series is an interesting one, although four out of the seven cases had a history of known demyelinating disease. Plus, the U.S. large observational study (which I also covered in the article mentioned earlier) did not find any association between mRNA vaccine and neurological disorders (e.g., acute disseminated encephalomyelitis, myelitis, encephalomyelitis, and transverse myelitis). While I'm not familiar with these neurological disorders, encephalomyelitis seems to be a type of demyelinating disease. I believe this observational study is a stronger form of evidence than the case series. 

Moving on, the main reason I'm responding is that I published this piece, "mRNA Vaccine and the Brain: A Recap and Update," two days ago. If anyone has feedback for this article, I'd greatly appreciate it. I can still put a short update in this article if needed. In a nutshell, the evidence still seems scarce, but we can still make some theoretical conclusions out of it. 

Have a pleasant weekend.

Kind regards,

Shin

[Wm. Stewart]

Thanks Shin for your continuing excellent presentation of extremely detailed information on an important subject. 

I find your analyses persuasive.

At the same time, keeping in mind the newness of the technology and complexity of the issue, I suggest we all remain open to any new developments or information on the question.

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