Why CFS and Long Covid patients need to aggressively support CRISPR gene editing for chronic viral infections

[gbells]

After contracting CFS/ME, having it for 16 years, and watching the field I am convinced that the only treatment that has any hope of widespread success is the CRISPR gene editing being done at the Fred Hutch Cancer Center on Herpes Simplex virus. Solve ME needs to partner with them to research gene editing for Epstein Barr virus, Human Herpes Virus 6/7 and cytomegalovirus.

The reason for this is because it is likely that ME/CFS originates from a viral superinfection that occurs when the immune system is weakened by Epstein Barr virus and/or Covid and which then allows other chronic viruses to overwhelm the body, trigger mitochondrial fragmentation in a large number of cells, and shuts down apoptosis which people perceive as the cessation muscle twitching and cold skin due to the inflammation from the viruses. This impairs mitochondrial energy production which results in ME and Long Covid, and sets people up for Non-Hodgkins Lymphoma type cancer. ME/CFS patients who develop cancer die at a younger age compared to the general population.

The average age of death for cancer in the general population is 72 years vs 47 years in ME/CFS patients. This is what we would expect when a large number of cells are immortalized and have blocked apoptosis from the viruses.

The idea of the research is to disrupt the viruses by inserting junk DNA code into their initiator sites to prevent them from functioning.

They have made significant progress but there is still much to be done for this to be a viable treatment.

https://www.fredhutch.org/en/news/r...iting-makes-progress-in-laboratory-studi.html

The biggest problems are to eliminate off target gene edits and to increase the kill percentage (currently 90%)

Anyone with the ability to push for this research should do so.

No other treatment approach is likely to help most CFS/ME/Long Covid patients.

Please email Solve ME at SolveCFS@SolveCFS.org and ask them to collaborate with the Fred Hutch Cancer Center on CRISPR gene editing for known ME/CFS viruses.

Open Medicine Foundation at Stanford is led by an expert in genetics, Ron Davis, so he should be very interested in this. On the other hand, given his lack of success at the foundation I'm not confident that he can pull it off. OMF's email is info@omf.ngo.

Tell them that any donations are contingent on them setting this up.

 

[Dysfunkion]

I unfortunately agree, I can micromanage all I want but this is just the equivalent of damage control at this point. I do just the wrong completely ordinary things and I'm not gonna be able to do anything anymore but sit in a chair or worse in bed rotting away in my room. My survival depends on minimizing all possible triggers and then managing them to death just so that I can continue to barely participate in life. I would pay all of my life savings just to get rid of this once and for all and function normally. If I get any good windows they are always fleeting and crashed down by the slightest ordinary thing I did. I literally can't live without lowering my baseline if get anywhere near a normal state. That's why at this point I also only have faith in genetic engineering, I'll keep trying new things with myself but like I said above this is all just damage control. I'm picking up the boxes off the floor of a factory that's seen multiple disasters where the machines barely work like they should. Maximizing the efficiency of that doesn't get rid of the broken machines.

 

[Wishful]

I'm not convinced that ME involves any chronic viral infections. I still think it's a feedback loop that's gone positive rather than negative, most likely involving glial cells. Chronic infections might make some people's ME symptoms more severe than if they didn't have that infection, but it wouldn't cure ME.

 

[cfs since 1998]

I'm not convinced that ME involves any chronic viral infections. I still think it's a feedback loop that's gone positive rather than negative, most likely involving glial cells. Chronic infections might make some people's ME symptoms more severe than if they didn't have that infection, but it wouldn't cure ME.

Evidence that viruses cause chronic disease is increasing, not just for ME/CFS but for other conditions, Multiple sclerosis, dementia/Alzheimer's, etc. Then there's Long COVID, obviously.

Also for those who say that the immune dysregulation causes the viral reactivations in ME/CFS, well, viruses like EBV directly dysregulate the immune system. They're viruses and they evolve faster than we do. EBV is a highly evolved virus that science still has a long way to go before understanding it fully.

I don't buy the "feedback loop" mechanism. That is not a model for any other disease, except psychological conditions. I don't believe it's possible for the body to get stuck in a hypometabolic/broken state all by itself.

 

[gbells]

@cfs since 1998,

Also for those who say that the immune dysregulation causes the viral reactivations in ME/CFS, well, viruses like EBV directly dysregulation the immune system.

I don't buy the "feedback loop" mechanism. That is not a model for any other disease, except psychological conditions. I don't believe it's possible for the body to get stuck in a hypometabolic state all by itself.

Excellent points.

The thing that's throwing people are the false negative antibody tests for EBV. Anyone who has a confirmed known history of mononucleosis is EBV positive regardless of what the antibody tests say.

EBV can remain dormant in the body and may not always be detectable through standard antibody tests, leading to these false negatives.

Dormant Epstein-Barr Virus (EBV) can indeed influence mitochondrial dynamics, including triggering mitochondrial fragmentation. EBV is known to manipulate mitochondrial function and dynamics through various mechanisms. For instance, it can interact with proteins like latent membrane protein 1 (LMP1) and dynamin-related protein 1 (Drp1), which are involved in mitochondrial fission and fusion processes12.

This manipulation can lead to mitochondrial fragmentation, which is often associated with cellular stress and dysfunction. Such changes in mitochondrial dynamics can contribute to conditions like chronic fatigue syndrome and other long-term health issues12.

 

[hapl808]

I don't buy the "feedback loop" mechanism. That is not a model for any other disease, except psychological conditions. I don't believe it's possible for the body to get stuck in a hypometabolic state all by itself.

That's what never quite rings true, although some of it could be semantics. People with HIV can manage the disease with medications, but getting rid of the infection entirely is more difficult. If we could eradicate HIV, would that fix the disease, or is there some feedback loop?

I really don't know - ME/CFS type symptoms can be triggered by so many different things that figuring out a definitive etiology is pretty difficult.

 

[wabi-sabi]

At this point, I'm not even convinced I have an ongoing infection. I just think my immune system has gone insane.

 

[cfs since 1998]

I've just discovered an older paper about EBV. It's not even about ME/CFS but rather infectious mononucleosis (IM) (glandular fever) -- but it contains some very interesting findings.

From Sauce 2006:

Acute primary EBV infection, when manifest as IM, appears to be unique in producing a global down-regulation of IL-15R on T cells and NK cells that lasts for many years after the disease episode.

They found this downregulation lasted up to 14 years. They compared this to cytomegalovirus (CMV) which did not appear to do long-lasting immune system damage.

Even in uncomplicated cases, the EBV-host balance remains abnormal for long periods after disease resolution and may never reach that typically struck after asymptomatic primary infection.

If it's that bad in "recovered" people, how bad is it in those with post-EBV ME/CFS?

A history of IM may carry with it other disease risks that have not yet been recognized.

In other words, symptomatic EBV infection might cause other diseases and we have no idea which ones.

The present work shows that symptomatic primary EBV infection leaves a long-lasting scar on the immune system.

Ah, but don't worry. Everyone has EBV, there's nothing to see here. Move on and do some amygdala retraining to fix your broken stress response. That will repair your immune system. (I know people wouldn't say that here, but that argument has been made...)

 

[Wishful]

I don't believe it's possible for the body to get stuck in a hypometabolic state all by itself.

I'm also not convinced that ME's core dysfunction is metabolic. As far as I can tell, my mitochondria have been producing ATP adequately, even when I feel really lousy. Maybe hypometabolism is a common downstream effect of ME, but that doesn't mean that it is an essential part of ME. If it was essential, why isn't it established as a biomarker?

The feedback loop I'm imagining might involve immune response, small clusters of neurons or glia, endocrine glands, or some other part of cells. Some molecular mechanism changes, and a feedback loop parameter becomes positive rather than negative, and gets locked into a state. It's possible to change a parameter in that loop to make it negative again, resulting in temporary remission, but other parameters are still set to reestablish the positive feedback, so we snap back into the ME state.

If it's not a model for any other disease, maybe that's because medical researchers don't look for such feedback loops. From an engineering perspective, the body looks like a bunch of interacting feedback loops. It's hard for me to think of that perspective of the body and not imagine some loops developing errors that result in positive feedback. A positive feedback loop fits my observations of my ME, especially regarding the abrupt switching of states. To me, that's a classic signature of a high-gain feedback loop.

 

[cfs since 1998]

I'm also not convinced that ME's core dysfunction is metabolic.

I didn't say that it was nor did I mean it like that.