40 replies to this topic

[Florin]

Besides the red flags about DRACO mentioned in another thread, here's some more red flags.

 

https://www.openphil...viral-treatment

[Hip]

Besides the red flags about DRACO mentioned in another thread, here's some more red flags.

 

https://www.openphil...viral-treatment

 

You can find a rebuttal of that article on the Kimer Med forum.

[Daniel Cooper]

I have recently started working for a company that is attempting to pick up where Rider left off with DRACO. Our goal is nothing less than the elimination of all viral disease in humans, pets and livestock.

 

We believe DRACO can become the world's first broad-spectrum antiviral drug.

 

We have already made considerable progress.

 

If you'd like to know more, or join us in our efforts:

 

https://kimermed.co.nz/landing

 

 

Clearly the world is in need of a broad spectrum anti-viral.  I mean, as stylish as I look in my covid mask, these things do get a bit tiresome.

 

Antibiotics revolutionized the treatment of bacterial diseases.  This has the same potential to treat that other scourge of infectious diseases - viruses.

[gbells]

I've been told that Todd Rider participates on this forum.  I emailed him the following message but he can reply here if he prefers.

 

 

 

A number of us on the Myalgic Encephalomyetis forum Phoenix Rising are discussing DRACO's potential to help with ME. What we see with the condition is that it is caused by multiple coinfections of apoptosis inhibing viruses including (HHV6, EBV, CMV, varicella zoster, and non-cytolytic coxsackie enterovirus). The prevalence of EBV is high, 80% in ME patients posing a problem with using for EBV infected patients because EBV blocks the assembly of the DISC protein needed to trigger the signal for necroptosis. After reviewing your PLOS1 paper on the subject it seems you may have tested it on EBV but it didn't work. Did you ever try DRACO on EBV infected cells? Do you think DRACO would work for any of the over viruses listed above? Thank you in advance.

 

[Kimer Med]

I've been told that Todd Rider participates on this forum.  I emailed him the following message but he can reply here if he prefers.

 

One of the mods would know better than me, but I've been a member here for years, and I've never seen any posts from Rider. In fact, I recall that someone here was trying to reach him a number of years ago for an interview or something, but AFAIK, he never responded.

 

I have personally tried to reach him through a bunch of different emails, as well as through his former staff at MIT/LL. He apparently didn't leave forwarding contact details, and no one there seemed to know how to reach him.

 

Having said that, I can try to answer your question, if you're interested. I've registered at Phoenix Rising, but my account hasn't been approved, so I can't post there yet.

[gbells]

Sure, just answer it here.  His PLOS1 paper said that it worked for 15 viruses but didn't list Epstein Barr Virus as one it could cure.  That got my interest because EBV is a very common virus but has an apoptosis blocking mechanism that prevents assembly of the DISC protein necessary to trigger RIP to trigger necroptosis that DRACO uses.  This makes me think that it won't be effective in 80% of the population who has EBV.  Since EBV is very common I was wondering if he ever tested it on EBV and didn't report the result which would seem to be failure.

Edited by gbells, 11 September 2020 - 11:05 PM.

[Kimer Med]

Sure, just answer it here.  His PLOS1 paper said that it worked for 15 viruses but didn't list Epstein Barr Virus as one it could cure.  That got my interest because EBV is a very common virus but has an apoptosis blocking mechanism that prevents assembly of the DISC protein necessary to trigger RIP to trigger necroptosis that DRACO uses.  This makes me think that it won't be effective in 80% of the population who has EBV.  Since EBV is very common I was wondering if he ever tested it on EBV and didn't report the result which would seem to be failure.

 

Necroptosis is a form of programmed cell death that results in necrosis. In necrosis, a cell effectively lyses and releases its interior contents to the surrounding environment. Because of that, necrosis activates the immune system, causing inflammation and other downstream effects. As I explain in my thread here:

 

https://forum.kimerm...ose-draco-work/

 

we don't want necrosis, and DRACO doesn't use necrosis. Therefore, the necroptosis pathways don't matter. Necroptosis is also known as "Caspase Independent Cell Death" (CICD). DRACO actually relies on Caspase *dependent* pathways.

 

Dr Rider reported success against 15 viruses. As a scientist and researcher, finding a virus that didn't respond as expected to DRACO would have been an important result, and would not have diminished his work in any way. There's no indication in his paper or elsewhere that he tested for it and didn't report a negative. In fact, in his 2015 crowdfunding pitch, he explicitly mentions wanting to test against Herpesviruses, including EBV:

 

https://www.indiegog...t-all-viruses#/

 

There would be no reason for him to propose that if he had already done the work.

 

"DRACO" is actually a family of compounds. One formulation, PKR+Apaf, works on the apoptosis side by activating Procaspase 9 (which then activates Caspase 9 --> Caspase 3). It turns out that EBV also activates Caspase 9, but without triggering apoptosis. On that basis (rather than on the TRIF / RIP side where EBV also interferes), it is possible that PKR+Apaf may not be effective against EBV. We won't know for sure until we test it (although in the Herpesvirus family, CMV is currently a higher priority for us than EBV, due to its probable effects on aging).

 

Even though EBV interferes with the Caspase 9 pathway in some way, that alone isn't reason enough to say for sure that PKR+Apaf won't work. Let's not forget the PKR half of the protein. The process of DRACO binding with dsRNA by itself also interferes with viral replication, even if apoptosis isn't triggered. If replication is slowed down enough, it's possible that the compounds interfering with Caspase 9 will fade faster than DRACO does. Rider showed that a single dose of DRACO lasts for at least 8 days in some cells, and of course in a therapeutic situation, multiple doses are possible. Again, we won't know for sure until we test. Which we're going to do.

 

In addition, if EBV does manage to evade PKR+Apaf, other formulations are possible. Rider tested PKR+FADD, for example, which works by activating Procaspase 8 --> Caspase 3, entirely bypassing Caspase 9. Using PKR+Caspase 3, which is the immediate precursor to the protein cleavage that results in cell death, may also be possible. Using RNase L instead of PKR is another possibility (which Rider also tested). It may produce different results because RNase L acts to degrade the dsRNA, hopefully crippling the virus in the process, while it's also working to cause apoptosis.

Edited by Kimer Med, 12 September 2020 - 01:23 AM.

[gbells]

Necroptosis is a form of programmed cell death that results in necrosis. In necrosis, a cell effectively lyses and releases its interior contents to the surrounding environment. Because of that, necrosis activates the immune system, causing inflammation and other downstream effects. As I explain in my thread here:

 

https://forum.kimerm...ose-draco-work/

 

we don't want necrosis, and DRACO doesn't use necrosis. Therefore, the necroptosis pathways don't matter. Necroptosis is also known as "Caspase Independent Cell Death" (CICD). DRACO actually relies on Caspase *dependent* pathways.

 

Dr Rider reported success against 15 viruses. As a scientist and researcher, finding a virus that didn't respond as expected to DRACO would have been an important result, and would not have diminished his work in any way. There's no indication in his paper or elsewhere that he tested for it and didn't report a negative. In fact, in his 2015 crowdfunding pitch, he explicitly mentions wanting to test against Herpesviruses, including EBV:

 

https://www.indiegog...t-all-viruses#/

 

There would be no reason for him to propose that if he had already done the work.

 

"DRACO" is actually a family of compounds. One formulation, PKR+Apaf, works on the apoptosis side by activating Procaspase 9 (which then activates Caspase 9 --> Caspase 3). It turns out that EBV also activates Caspase 9, but without triggering apoptosis. On that basis (rather than on the TRIF / RIP side where EBV also interferes), it is possible that PKR+Apaf may not be effective against EBV. We won't know for sure until we test it (although in the Herpesvirus family, CMV is currently a higher priority for us than EBV, due to its probable effects on aging).

 

Even though EBV interferes with the Caspase 9 pathway in some way, that alone isn't reason enough to say for sure that PKR+Apaf won't work. Let's not forget the PKR half of the protein. The process of DRACO binding with dsRNA by itself also interferes with viral replication, even if apoptosis isn't triggered. If replication is slowed down enough, it's possible that the compounds interfering with Caspase 9 will fade faster than DRACO does. Rider showed that a single dose of DRACO lasts for at least 8 days in some cells, and of course in a therapeutic situation, multiple doses are possible. Again, we won't know for sure until we test. Which we're going to do.

 

In addition, if EBV does manage to evade PKR+Apaf, other formulations are possible. Rider tested PKR+FADD, for example, which works by activating Procaspase 8 --> Caspase 3, entirely bypassing Caspase 9. Using PKR+Caspase 3, which is the immediate precursor to the protein cleavage that results in cell death, may also be possible. Using RNase L instead of PKR is another possibility (which Rider also tested). It may produce different results because RNase L acts to degrade the dsRNA, hopefully crippling the virus in the process, while it's also working to cause apoptosis.

 

I see he has two pathways targeted.  Apaf that triggers BID, and FADD which triggers necroptosis.  Both would definitely be blocked by EBV's inhibitors (Apaf blocked by Nf-kB and FADD blocked at DISC.  Perhaps this is why he can't get it funded.  It would only work on the 20% of people without past EBV infection.

Edited by gbells, 12 September 2020 - 04:20 PM.

[Hip]

 It would only work on the 20% of people without past EBV infection.

 

Even if it were the case that EBV can block cell suicide in a way that makes DRACO less effective, or ineffective (and it remains to be seen if that is the case), how do you arrive at the conclusion that DRACO or VTose would not work for the 90% of adults who have had a past infection of EBV?

 

 

When EBV goes into latency, it resides in certain cell types, including B-cells. However, I believe it is only a very tiny percentage of cells that will contain latent EBV.

 

This paper for example says "the frequency of EBV-infected cells was 800/10⁶ in the G0-G1 population" of B-cells. So less than one in every thousand B-cells contains EBV. I expect vast majority of cells in the body will not contain latent EBV.

 

Thus EBV would not interfere with DRACO or VTose's ability to fight acute viral infections, even if EBV could hinder DRACO's mechanism of apoptosis. 

 

And it in terms of the low-level chronic non-cytolytic enterovirus infections linked to several diseases, including type 1 diabetes, which produce a very small amount of dsRNA and so could be amenable to DRACO treatment, EBV would not prevent DRACO or VTose from fighting those, except perhaps in rare cells which might have an EBV co-infection.

[gbells]

It depends how many EBV infected cells you are talking about.  One theory of myalgic encephalomyelitis is that the problem is that if someone is recovering from EBV and has not yet developed antibodies another viral co-infection further weaken immunity and allow both organisms to spread faster and deeper than one alone.  If someone had EBV it would be a safe harbor for other DRACO target viruses and you would need to dose DRACO long enough for the body to build up a natural immunity to the invader because when you stopped DRACO and there were no antibodies it would become active again.  Anyway, good comments.  Thank you for helping me understand the drugs.

 

 

[gbells]

I did some more research on the DRACO approach. Neither FADD or Apaf will work for many people because they hang up at Active caspase-3 blocking by HHV6 (a common virus). If you could introduce either a pro-caspase 7 or active caspase 7 it would trigger parp if you blocked Nf-kb which is upregulated by EBV (easy to do with turmeric). Both EBV and HHV6 are common chronic viruses. Can you attach a form of caspase 7 (pro or active) to the PKR protein instead of FADD/Apaf? That would fix.