PRO HEALTH’S BIG ANTIVIRAL TRIAL COULD USHER IN NEW TREATMENT ERA FOR FIBROMYALGIA
From the News Desk of Jeanne Hambleton
By Cort Johnson • http://www.ProHealth.com •
Two articles March 8, & June 18 2014
Reprinted with the kind permission of Cort Johnson and Simmaron Research.
If you are looking for some promising news about fibromyalgia do not miss the two articles below by Cort Johnson of Health Rising, posted on the well-known American ProHealth site founded by and courtesy of Rich Carson. This is certainly a site to watch.
The first article appeared in March and now we have a follow up, with a video online dated June 18. Worth a read. Jeanne.
A New Approach to Fibromyalgia
Infections are a common trigger for fibromyalgia (FM), and fibromyalgia patients experience many ‘sickness behavior’ symptoms, but we haven’t usually associated FM with viruses or immune system problems.
That has been changing recently. An immune biomarker has been proposed. Small fiber neuropathy – possibly caused by immune dysregulation – has been found. Dr. Dantini has been treating FM with antivirals for years. The immune system is starting to get some respect in FM.
Now, in a surprising twist, it is going to be fibromyalgia rather than chronic fatigue syndrome, that is getting the big, placebo controlled, double-blinded multi-center antiviral trial.
Last year we heard that Dr. William Pridgen in Alabama was getting his ducks in a row for a major antiviral trial. Four weeks ago in an email exchange he confirmed that the money – $3.3 million dollars – all gathered from ‘angel investors’ is in hand, and the four-month 143 patient trial began in early October.
Pridgen’s Innovative Med Concepts biotech startup is producing the study.
A Different Path
The pathways researchers and doctors take to get to disorders like FM or chronic fatigue syndrome are nothing but diverse, and it is worth taking a look at how Dr. Pridgen, a surgeon, who came to fibromyalgia. (Dr. Julia Newton’s pathway to ME/CFS was through elderly people experiencing dizziness and to her surprise, a great deal of fatigue.) Dr. Pridgen’s pathway to fibromyalgia was through the gut.
Pridgen saw a pattern emerge in his treatment of thousands of patients with chronic gastrointestinal issues that intrigued him. A patient would get better, but then experience a stressful event that would send him/her back into the soup. They would get better, but during the next relapse they would stay sick longer and their recovery period would be shorter. Eventually they would be sick all the time.
The problem, he thought, had to be some sort of pathogen that was steadily increasing with every recurrence. Giving his patients antivirals helped, but problems remained. Then he found that adding an anti-inflammatory (which also had anti-viral properties) reduced their fatigue, gastrointestinal complaints, depression and anxiety markedly and improved their energy.
An observational study indicating that the combination drug approach had a 90% ’efficacy rate’ led Pridgen to start a company, enlist investors and create the large treatment trial.
Pridgen’s theory fits glove and hand with several other fibromyalgia/chronic fatigue syndrome theories. As with Van Elzakkers’ vagus nerve infection theory for ME/CFS, Pridgen’s theory begins with a nerve-loving virus that takes up residence – for life – in nerves in the sensory ganglia found across the body.
Instead of HHV6 or EBV Pridgen believes herpes simplex viruses, are the key in FM/ME/CFS. Other than a 1993 theory proposing herpes simplex virus was at play in ME/CFS, interest has been scanty. HSV-1′s ability to affect many of the genes and gene pathways suspected of playing a role in nervous system disorders such as Alzheimer’s, Parkinson’s, depression, chronic fatigue syndrome and autism, however, led one researcher to propose it could play a role in all of them.
HSV-1 has been found in the esophagus, stomach and duodenum of the gastrointestinal system. In fact, HSV-1 was proposed to cause ‘recurrent functional gastrointestinal disorders’ such as IBS, as far back as 1996.
Pridgen’s patent application indicates that he believes that stressors and peptides and hormones released by the sympathetic nervous system and HPA axis set the stage for herpes simplex-1 reactivation. Pridgen proposes that repeated HSV reactivation could kill the sensory nerve cells (small fiber neuropathy?) and destroy part of the nerve ganglion. (Stress induced HSV-1 reactivation has been documented in laboratory animal studies.)
Once these neurons and ganglia are damaged, Pridgen believes they send out signals that ultimately muck up the pain processing centers in the central nervous system. The over-generation of neurotransmitters such as glutamate, Substance P, serotonin, norepinephrine, dopamine, brain-derived neurotrophic factor (BDNF) involved in this process then causes central sensitization.
Antiviral Plus
Pridgen proposes to stop the viral reactivation and the central sensitization with antivirals; an approach that has been tried before in chronic fatigue syndrome, but not in the way Pridgen’s doing it.
One of Pridgen’s patent applications suggests that one of his unique insights has been to combine valacyclovir (valtrex) with an anti-inflammatory, Celecoxib (Celebrex) that has antiviral properties. Other combinations are being tested and Pridgen stated they have not released the make-up of the IMC formulation used in the trial. It is not clear, then, what drugs at what doses were used in the study or which will prove most effective.
Celexcoxib (Celebrex) is a non-steroidal anti-inflammatory (NSAID) COX-2 inhibitor usually used in the treatment of osteoarthritis, rheumatoid arthritis, acute pain, painful menstruation and menstrual symptoms. It down regulates the activity of inflammation producing cells.
Pridgen proposes that the two drugs hit the virus at different stages of its life cycle. Pummeling the virus with that one-two punch, he believes, will finally stop the virus from reactivating.
Pridgen and Duffy are looking for herpes simplex virus, but other herpes viruses could be affected by this treatment. We would not know if they are until further studies are done.
Inflammation Gone Awry
Pridgen and his partner, molecular virologist, Carol Duffy will also attempt to develop a diagnostic test for fibromyalgia using cytokine arrays they believe will document high levels of pro-inflammatory cytokines and low levels of anti-inflammatory cytokines.
Like VanElzakker, Pridgen believes the body is over-reacting to the virus.
“It is basically exaggerating its reaction to the virus. Any little stress reactivates the virus, and, rather than the body saying, ‘Oh, this is just a virus I have been living with this since I was five,’ the body keeps saying, ‘Oh, my God,’ and throws on all this inflammation, and that gives these people this pain.”
“There is a theory that all pain, one way or another, is inflammation,” Duffy says. “It is inflammation gone awry.”
Not just Fibromyalgia
Pridgen and Duffy have their eyes on more than Fibromyalgia. Pridgen’s provisional patent proposes this treatment will work for chronic fatigue syndrome, irritable bowel syndrome, chronic pain, chronic headache, chronic neck pain, chronic back pain, chronic depression, chronic clinical anxiety disorder, post-traumatic stress disorder (PTSD), brain fog, cognitive dysfunction and chronic interstitial cystitis.
Celebrex – The Antiviral?
We do not hear anything about Celecoxib as a virus fighter in ME/CFS, but some evidence suggests it could be efficacious against herpes simplex virus. The ability of COX-2 inhibitors to decrease prostaglandin production is believed to push the immune system towards a Th1 (antiviral) response and away from the Th2 response often found in ME/CFS.
Celebrex was shown to reduce stress-induced herpes virus reactivation in the nervous systems of mice. Another study found that reactivation of HSV-1 in mice was associated with upregulation of COX-2 gene expression in their nerve ganglia. HHV-6 can also induce COX-2 expression. Both COX-1 and COX-2 are needed for viral replication.
(One mother found that VIOXX (now off the market) reduced her daughters IL-6 levels and eliminated the ‘panic attacks’ she had experienced following a central nervous system infection.)
(Aspirin and flavanoids, vitamin E and fish oils also inhibit COX-2. The efficacy some ME/CFS patients experience from using omega-3 fatty acids could be due to antiviral effects.)
Tissue Biopsies
Along with treating the virus, Pridgen and his partner, molecular virologist Carol Duffy, will be using PCR to test for the virus, not in the blood, but in gut tissue samples.
One of the most intriguing aspects of the Pridgen-Duffy study is the search for HSV-1, not in the blood, but in the tissues. We know the Chronic Fatigue Initiative’s Pathogen study failed to find evidence of viral infection in the blood. Now, Pridgen and Duffy are testing gut samples for herpes virus simplex in their study.
First PCR will be used to search for herpes viruses in both the control and FM gut samples. Then antibodies will be used to determine if an active infection is present. In subsequent studies, electron microscopy will look for the herpes viruses particles themselves.
In preliminary studies, 18/19 fibromyalgia patients with gut issues contained herpes simplex virus DNA in their gut tissues. No other herpes viruses were found. Immunoblot testing indicated that an active infection was present in eight of nine positive biopsies.
Dr. Pridgen reported in an email they are still trying to determine the optimum dose and cautioned everyone to wait until the results of the Phase 3 trial are done before starting this treatment. He also stated he feels they are ‘very close’ to helping many people with this condition. The results of the trial are expected to be released in mid-year.
Conclusion
Pridgen and Duffy’s big multi-center antiviral trial in Fibromyalgia is nothing if not exciting in its scope and approach. Pridgen’s ability to come up with over $3,000,000 in startup funding suggests he and Duffy have got some solid data backing their trial up.
If the results are positive, Pridgen and Duffy could usher in an entirely new way of treating both fibromyalgia and chronic fatigue syndrome.
LATEST REPORT
Brief Report from Dr. Prigden on the Fibromyalgia Antiviral Trial three months later
By Cort Johnson • http://www.ProHealth.com • June 18, 2014
Reprinted with the kind permission of Cort Johnson and Simmaron Research and courtesy of ProHealth & Rich Carson.
Brief Report From Dr. Prigden on the Fibromyalgia Antiviral Trial – and the Future Chronic Fatigue Syndrome One
It is not too much to say that if successful, the Pridgen antiviral trials for Fibromyalgia would be a paradigm changer – turning FM from a poorly treated central nervous system disorder to a disorder characterized by a (hopefully) treatable herpesvirus infection.
Pridgen’s approach is new in several ways. Not only has no one targeted herpesviruses in FM before, but the herpesvirus Pridgen is targeting, herpes simplex virus, is one no one has connected with either FM or ME/CFS before.
Pridgen has combined an antiviral with an anti-inflammatory (with antiviral properties). Rumors have abounded regarding the identity or identities of the drugs, but we will not know officially which they are until the report is made.
The fact that we have not had a press release by now regarding the Phase II trial has led to some concern. (Phase two trials are typically larger trials (1-several hundred people) that further assess a treatment’s efficacy and safety. Pridgen’s Phase II trial was a large multi-center trial.)
I contacted Dr. Pridgen to see what he could say at this point. This is what he said.
• They hope to present their research mid-Nov.
• A press release will predate that.
• The treatment was statistically significantly effective in improving nearly every primary and secondary endpoint.
• The treatment was significantly superior to placebo (p<.oo1) (not sure which endpoints).
• The treatment was better tolerated than placebo.
• The results in the FM trial are good enough that preliminary plans are being made for toxicology studies that will allow them to move forward on a similar Proof of Concept Phase 2 CFS (ME/CFS) trial; i.e. they are beginning to work on a similar ME/CFS trial.
• They will be looking for government/humanitarian funding for that.
The Earlier Video
Check out a confident Dr. Pridgen as he talks about the Fibromyalgia trial sometime around April at a local news station.
(The video is available on the website to view – courtesy of ProHealth. Log on to –
http://www.prohealth.com/library/showarticle.cfm?libid=19014)
Conclusion
It is going to take longer for the final results than many had hoped but the news otherwise is good. The significant improvement in almost all the endpoints is promising (and I would say somewhat unusual). The fact that they are beginning preliminary planning for an ME/CFS trial suggests that the FM trial went well indeed.
Still, we will not know how significant the significant improvements are until the press and study release probably in November.
That will be frustrating to those who want to get going on treatments now, but my understanding is that this period – prior to publication – is a delicate period in the development of any drug. If that is true, think how much more so it is for a startup company that is going to need to raise significant funds for the big Phase III trial. Publicly releasing the full results and the drug combo they have identified this far in advance of publication would be a mistake.
For more on Pridgen’s antiviral trial check out:
•Big Antiviral Trial Could Usher in New Treatment Era for Fibromyalgia – http://simmaronresearch.com/2013/12/big-antiviral-trial-era-fibromyalgia/
Watch this space next November.
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About the Author: Cort Johnson has had ME/CFS for over 30 years. The founder of Phoenix Rising and Health Rising, Cort has contributed hundreds of blogs on chronic fatigue syndrome, fibromyalgia and their allied disorders over the past 10 years. Find more of Cort’s and other bloggers’ work at Health Rising.
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