Dr. Pridgen's 9 different cocktail mix patents & research under Dr. Carol Duffy name

[Jonathan Edwards]

It will be interesting to see where all this will lead. At least it's a research study that is away from psychsocial model of CBT/GET and PACE and hopefully get researchers to think outside the box and open the entrenched mindset among those in the medical profession concerning Fibro, GWI, and ME/CFS.

I fear it will lead nowhere unless there is better trial design. In science it makes no difference what theory you prefer in advance - as you say that is mindset. All that matters is that the experiment is designed well enough to test the theory. The PACE trial was weak on blinding. This study looks to be equally weak on a needed control group. So the delegates at the ACR meeting will pass it by.

I know hundreds of these ACR delegates and in fact I do not think they have an entrenched mindset about ME. I think most of them would say 'well, we haven't a clue have we?'. If someone comes up with a new treatment shown to be effective in a well designed trial they sit up and say 'gosh that's interesting' - I know that because I have been around chatting about rituximab. The rituximab phase II result is inconclusive but at least the trial was designed properly.

We need to encourage ME researchers to compete at a convincing level in terms of trial design. That is the only way to get progress.

 

[Marco]

My thought is that the combination might be working through mechanisms that have been investigated for a long time - pain relief by celecoxib as a Cox-2 inhibitor.

Or as another microglia inhibitor?

Cyclooxygenase-2 mediates microglial activation and secondary dopaminergic cell death in the mouse MPTP model of Parkinson's disease

"In several epidemiological studies, nonsteroidal anti-inflammatory drugs have shown protective effects in reducing the risk of neurodegenerative disease such as Alzheimer's disease [8,18] and PD [19]. In the present study, we tested the hypothesis that excessive COX-2 aggravates MPTP-induced toxicity by perpetuation of the inflammatory response, which leads to secondary neuronal cell death in the SNpc. This study was designed to explore the role of COX-2-related inflammation in the pathogenesis of PD and to test the possibility of COX-2 inhibitors as a potential therapeutic drug for PD.

Using an MPTP mouse model, C57BL/6N mice treated with therapeutic doses of valdecoxib showed improved cellular survival and behavioral function compared to vehicle controls. Similar results were obtained using COX-2-deficient mice. Both inhibition of COX-2 and genetic deficiency of COX-2 reduced SNpc microglial activation and mitigated MPTP-induced neurotoxicity on dopaminergic neurons in the SNpc."

http://www.jneuroinflammation.com/content/3/1/6

 

[Jonathan Edwards]

Or as another microglia inhibitor?

Certainly.

 

[Jon_Tradicionali]

Or as another microglia inhibitor?

Likely.

But the question still stands why the results were not seen until Famciclovir was added.

Considering it takes 3-6 months to work, that suggests the combination blocks pro-inflammatory cytokines as sickness behaviour symptoms induced from cytokines in cancer patients are seen within mere hours but even after chemo is stopped, cytokine profile does not normalise until 3 months after and only then do the symptoms also disappear. Link posted in my previous post.

 

[Jon_Tradicionali]

For someone who commented above regarding MS. The similarities between MS and CFS are uncanny. They cannot be denied, especially brain matter changes.

"Thus, several lines of evidence suggest that microglial activation initiated by neuronal damage may be toxic and persistent, continuing long after the initiating damaging/toxic stimulus is gone."

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2951017/

The above refers to PD/MS/AD which of course have much relation to CFS.

An infectious assault can be cleared by the immune system but still prompt chronic microglial activation.

 

[alex3619]

@Ecoclimber, the thing is this was a phase IIa trial. Its not the full thing. Their goals would have been focused on things like safety, for which they had good results. I am guessing the possibly $100 million phase 3 price tag comes with many more study arms, many more patients, and a lot more tests, over a longer time, and with more extensive analysis.

Far too often studies in ME are limited by the available funding. So they tend to be modest. Which makes them studies that are not as scientifically sound as they should be. Compromises get made. This does not however mean that a phase 3 trial will be accepted without sound design.

@Jonathan Edwards is right that getting the design to test the hypothesis effectively is very important. If we have a phase 3 trial with an unsound design, no matter the results we will wind up with a situation that we need yet another trial, with another bunch of years delay before treatment can be made available around the world.

 

[Jonathan Edwards]

@Ecoclimber, the thing is this was a phase IIa trial. Its not the full thing. Their goals would have been focused on things like safety, for which they had good results. I am guessing the possibly $100 million phase 3 price tag comes with many more study arms, many more patients, and a lot more tests, over a longer time, and with more extensive analysis.

I am interested to know just what does justify a $100 price tag, Alex. The last proof of concept four arm multicentre efficacy trial I was involved in used a very expensive drug and cost €2M, not €100M. The current trial has no safety value because the safety issues are around uncommon but devastating effects of Cox-2 inhibitors, as you know. That sort of safety can only be judged from phase 4 or post marketing surveillance.

 

[Marco]

But the question still stands why the results were not seen until Famciclovir was added.

As we know other antivirals have a (possibly more direct) attenuating effect on microglia the effects could be additive and it may take a prolonged period for activation to die down with potentially a threshold effect?

 

[alex3619]

I am interested to know just what does justify a $100 price tag, Alex.

I have been wondering about that myself. Its a LOT of money. Its twenty times the government funding for ME/CFS per year. It certainly wont be coming from patients. Its entirely possible the figure is wrong. Or part of a marketing ploy.

 

[lansbergen]

or post marketing surveillance.

And that is very important. I remember when the med I use was put on the market the pharm com asked for feedback. That showed there was a problem in a certain dog breed that had not showed with the dogs they did the trials on.

 

[boohealth]

Discovered and proven, no. But undiscovered or unproven? We don't know.

Well, there could be a flat planet somewhere too, it hasn't been disproven
The null hypothesis can never totally be disproven. Bigfoot--even if you disprove every track thought to be bigfoot, and every story of bigfoot, you haven't disproven bigfoot. A bigfoot could still be discovered, right?

 

[alex3619]

Well, there could be a flat planet somewhere too, it hasn't been disproven
The null hypothesis can never totally be disproven. Bigfoot--even if you disprove every track thought to be bigfoot, and every story of bigfoot, you haven't disproven bigfoot. A bigfoot could still be discovered, right?

Lol, in many ways I agree with this, but I don't want to get into the subject of proof on this thread. Bigfoot might indeed be out there.

 

[JT1024]

I cannot read the entire thread... I am sorry. I have limited time to be able to read.

One poster indicated that the clinical trial to date did not measure up to his standard.

#1, this is the US, not the UK. Not sure if there are differences in approvals of drugs but it is to be considered.
#2, the addition of the antiviral did not take months to see a huge gain. In my own personal experience, the results were immediate - even though I was not on the antiviral that provided the optimal response and the best dosage is still to be determined.
#3, the effectiveness seemed to be from the dosaging from the anti-viral, not celebrex. I could be wrong on this but I'm too tired to investigate further.

I am THRILLED to have a treatment option that offers relief. While fine-tuning is necessary through Phase 3 clinical trials and perhaps investigation into why these combinations have worked, I am hopeful.

Minimal gains have been realized through prior treatments.

 

[Daffodil]

I really hate taking anti inflammatories, but would of course do it given the alternative! It can cause heart problems and clotting issues. I have a friend who was on them for decades due to Reiter's and now he has severe DVT.

I am on Celebrex right now and am about to start another. I am not sure if they help...I don't think I notice much difference.

Here is an interesting article showing that some NSAID's actually have an effect on EBV early antigen expression...wonder if that's why they are being prescribed! I don't think regular antivirals effect early antigen expression.

http://www.ncbi.nlm.nih.gov/pubmed/11090973