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Treatment Resistant Depression or Chronic Fatigue Syndrome? Child Psychiatrist Finds Success With Antivirals

September 23, 2014

A Different Kind of Psychiatrist

“I have now treated dozens of adults and adolescents who came to me with the diagnosis of “treatment-resistant depression” and instead they had Chronic Fatigue Syndrome. With proper treatment, this viral illness can be successfully controlled.”

ted-henderson

Dr. Henderson is one of the rare psychiatrists to acknowledge the role the immune system and viruses can play in producing symptoms many associate with psychiatric disorders like fatigue

Chronic Fatigue Syndrome in all its forms is difficult to treat, but one doctor in Centennial, Colorado is apparently having some success with antivirals. Dr. Theodore Henderson is not a virologist or even an infectious disease specialist. He’s a child psychiatrist – perhaps the last profession one might expect to be open to viral theories of ME/CFS or childhood depression.  (I remember Environmental Medicine specialist Dr. William Rea telling me that he could count on the fingers of one hand the number of psychiatrists who didn’t believe environmental illness was mental.)

On his website Dr. Henderson descries the DSM approach that attempts to pigeonhole patients and put them in one category or the other. Instead he tries to approach the neurobiological problems of each patient uniquely.

I approach psychiatry from a brain-based biological perspective.. Most people cannot be pigeon-holed into a single category and most psychiatric conditions are actually a range of disturbed neurobiological processes. As a result, I approach each patient, child or adult, as an individual with a unique brain.

While Dr. Henderson uses traditional approaches to treat mental  disorders, he also recognizes the role the immune system and  viruses can play in producing some psychiatric symptoms.

“More importantly, growing evidence suggests that not all psychiatric symptoms, such as anxiety, fatigue, listlessness, low mood, or poor concentration, result from intrinsic flaws in the patient’s brain. Extrinsic causes, such as infections and toxins, can cause these psychiatric symptoms. The resulting cluster of symptoms might mimic anxiety, depression and other psychiatric disorders, leading to misdiagnosis and ineffective treatment.

Certain rare autoimmune disorders can lead to the formation of antibodies against specific neurotransmitter receptors. Much more widespread autoimmune disorders, such as systemic lupus erythematosus, can lead to cognitive changes, anxiety, seizures, and mood disorders”

Dr. Henderson reported he has been effectively treating both adolescent and adult Chronic Fatigue Syndrome patients with antivirals for several years. He recently published a paper describing his results with adolescents.

The Paper

Henderson TA.  Adv Mind Body Med. 2014 Winter;28(1):4-14. Valacyclovir treatment of chronic fatigue in adolescents.
pathogens

Dr. Henderson cites Dr. Lerner’s work with antivirals and ME/CFS on his website

In the paper, Dr. Henderson first cites the low diagnostic rates for Chronic Fatigue Syndrome (20%).  Then he argues that studies suggest reactivated herpesvirus infections, particularly HHV-6, are common in ME/CFS.  Arguing – as did Dr. Brewer at the Simmaron Research Foundation’s Immunology Workshop in San Francisco – that IgM antibodies are not diagnostic in this disease, Dr. Henderson asserted that primary cell cultures in combination with antibody or PCR tests indicate HHV-6 infection rates are very high in ME/CFS.

The Antiviral Subset?

In Dr. Henderson’s experience (approximately 65 patients treated) ME/CFS patients whose illness began with flu-like onset and who have:

  • have elevated IgG levels against a herpesvirus
  • low natural killer cell activity
  • high ribonuclease activity
  • high levels of angiotensin converting  enzyme (>35)
  • high TNF-a levels
  • elevated total IgM or IgG levels

responded well to antivirals.  He undertook a retrospective chart review of 15 adolescents he had treated with valacyclovir (Valtrex) between 2007 and 2013.

Valtrex is used to treat herpes zoster and herpes simplex and, in Chronic Fatigue Syndrome, Epstein-Barr Virus reactivation. Two studies by Lerner suggest Valtrex can be effective in ME/CFS.

young-man

Many of the adolescents who responded to antivirals had been referred to Dr. Henderson for treatment resistant depression

Dr. Henderson evaluated these patients like any good child psychiatrist would: He looked for mood disorders, a history of childhood abuse, assessed their sleep quality, and reviewed their school performance. He looked for any other significant symptoms and did laboratory work.  He noted that most of them had been referred to him for having ‘treatment-resistant depression’. All experienced fatigue, low motivation, academic problems, and unrefreshing sleep. Most had tried antidepressants or other mood altering drugs without effect. They did not, however, meet the CDI self-report test for depression.

Upon further evaluation six were given a diagnosis of Chronic Fatigue Syndrome, four were given an ME/CFS diagnosis plus anxiety, and three were given a diagnosis of ME/CFS diagnosis plus mood disorders.

Eleven were receiving failing grades in at least one class, and almost half had dropped out of school.  A third were sleeping more than 12 hours a day.

Ten could remember an infectious event they didn’t recover from.  Interestingly, a third of the group reported that they had always experienced significant fatigue.

fatigued-young-woman

The fatigue levels of his young patients were incredibly high

Their self-reported fatigue levels were almost off the charts.  While ‘significant fatigue’ is indicated by a score of 39 on the Fatigue Symptom Index (FSI), their mean score was 95. Similarly, they topped out on the Fatigue Severity Scale with almost two-thirds of the participants scoring near maximum fatigue levels (56 out of a possible 63).

The doctor provided them with the option of going on Valacyclovir, noting that the published evidence that it would work was small and confined to adults, not adolescents.  They began on an oral dose 500 mg BID and worked their way up to 1000 mg BID over a couple of weeks.

Results

“The medical understanding of CFS has been impeded to a degree by the resistance to the concept  of chronic viral infections of the central nervous system.”

Almost all of the adolescents responded quickly to the antivirals. Within three months 12 out of 15 reported greater than an 80% improvement in symptoms. After 8 months 14 out of 15 adolescents reported increased energy, improved sleep, increased motivation, and “return to normal functioning”. Ten of the 14 reported a “complete resolution of fatigue” and their depressive symptoms disappeared. Five of the seven who had dropped out of school returned to school and ultimately enrolled in college.

upwards graph

Fatigue scores generally dropped dramatically in response to antiviral therapies

The changes in the fatigue self-report scores were astonishing. Mean Fatigue Symptom Index (FSI) scores for nine of the fifteen dropped from the whole group FSI score of 56 to and FSI score of 12.  Fatigue Severity Scale scores dropped from 95 to 19. All ME/CFS symptoms measured by the MFSI dropped significantly.

The impressive results bring to mind Dr. Montoya’s initial Stanford valganciclovir trial in adults (9/12 recover) and the reminder that the results of his more rigorous double blinded, placebo-controlled trial, while positive, were much less successful.  Still, Dr. Henderson has clearly experienced real success with his adolescent ME/CFS patients, none of whom had responded to other approaches.

Noting that his adolescent patients were more likely to have acute infectious onset than adults and less likely to experience depression, Dr. Henderson suggested adolescents might have more success with antivirals.

While he didn’t mention it, one wonders if late exposure to Epstein-Barr Virus is playing a major role in adolescent onset ME/CFS.  Adolescence is becoming a more and more likely time of first exposure to Epstein-Barr virus (EBV).  Early exposure to EBV (during childhood) often doesn’t cause symptoms, but as cytotoxic T-cells decline after early childhood, later exposure causes a much more virulent illness. Some researchers believe delayed exposure to EBV is behind the increased levels of autoimmune disorders seen.

As do some others in the field, Dr. Henderson, took issue with the medical community’s unwillingness to more fully investigate the impact central nervous system viruses have on a range of disorders including ME/CFS, multiple sclerosis, schizophrenia, Alzheimer’s, and Autism.

Follow-up

The average duration on the drug was over two years.  Four patients discontinued treatment after about 18 months and remained well at the time of this report. Five patients who discontinued treatment in a similar time frame, however, immediately relapsed and had to go back on the drug.

Treatment Resistant Depression = Chronic Fatigue Syndrome?

“The authors secondary hypothesis is that treatment-resistant depression may often, in fact, be CFS that has been misdiagnosed.”

Dr. Henderson proposed that a significant number of adolescents diagnosed with treatment-resistant depression actually have a form of chronic fatigue syndrome that may respond to antivirals.

question-mark

Remarkably, most of the adolescent referred to Henderson for treatment resistant depression….did not meet the criteria for it

The medical profession’s eagerness to diagnose adolescents experiencing severe fatigue with depression was evident. Despite the fact that most of his adolescent patients did not met the DSM criteria for depression nor did they have CDI scores consistent with depression, many of them were still diagnosed with depression.  Other findings, such as low cortisol and cerebral hypoperfusion, were at odds with a depression diagnosis, yet over half the adolescents had been treated for depression and had not responded.

One is reminded of the saying that if your only tool is a hammer, everything begins to look like a nail.  But Dr. Henderson’s specialty is psychiatry.  He recognizes true depression when he sees it.

In fact, adults with inflammation-associated depression who make up perhaps a third of all cases of depression – do not respond to antidepressants either. Interestingly, a subset of depressed patients without inflammation-associated depression get worse when given anti-inflammatories. (For them some inflammation is good!)

The doctor provided a case report involving an adolescent experiencing fatigue, brain fog, and depression diagnosed with ‘treatment resistant depression’ who had failed to respond to either SSRIs or SNRIds.  Tests showed she had reduced NK cell counts and high IgG titers to EBV and HHV-6. Three months after going on 1000 mg a day of Valacyclovir she had experienced a complete resolution of all her symptoms. Three months later, after forgetting her meds on a trip to Disneyland, her symptoms quickly returned and she spent most of the vacation in bed at her hotel. One week after resuming the medication her symptoms completely disappeared again.

Dr. Henderson proposed a placebo-controlled trial be done involving seropositive (antibody positive) and seronegative ME/CFS patients. The trial should not, he emphasized, employ acyclovir, an antiviral he asserted has low bioavailability and is rapidly eliminated by the body.

Conclusion

In a retrospective case analysis Dr. Henderson reported very high response rates to Valacyclovir (Valcyte) in a small group of adolescents with ME/CFS. Fatigue and other symptoms virtually disappeared for many in the study, a significant portion of whom had been diagnosed with treatment-resistant depression.

He proposed that that many adolescents diagnosed with treatment-resistant depression may have Chronic Fatigue Syndrome.  Dr. Henderson also suggested that the high incidence of infectious onset and low incidence of depression in adolescents with ME/CFS made them good targets for antiviral therapy.

Check out Dr. Henderson’s website and blog here.

 

 

 

 

 

 

 

 

Brief Report From Dr. Prigden on the Fibromyalgia Antiviral Trial – and the Future Chronic Fatigue Syndrome One

It’s 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.

Is it a breakthrough? The results look good so far - stay tuned!

Is it a breakthrough? The results look good so far – stay tuned!

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 also combined an antiviral with an anti-inflammatory (with antiviral properties).  Rumors have abounded regarding the identity or identities of the drugs, but we won’t know officially which they are until the report is made.

The fact that we haven’t had a press release by now regarding the Phase II trial has lead 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’re 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.

 

Conclusion

It’s 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’re beginning preliminary planning for an ME/CFS trial suggests that the FM trial went well indeed.

Still, we won’t 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’s true think how much more so it is for a startup company that’s going to need to raise significant funds for the  big Phase III trial.  Publicly releasing the full results and the drug combo they’ve 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

 A New Approach to Fibromyalgia

Infections are a common trigger for fibromyalgia (FM), and fibromyalgia patients are experience many ‘sickness behavior’ symptoms, but we haven’t usually associated FM with viruses or immune system problems.

woman questioning

So it’s going to be Fibromyalgia that gets the really big antiviral trial ….

That’s been changing  recently. A 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’s starting to get some respect in FM.

Now, in a surprising twist, it’s going to be fibromyalgia rather than chronic fatigue syndrome, that’s 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’s worth taking a look at how Dr. Pridgen, a surgeon, 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.

virus

Shorter and shorter relapses over time in his patients lead Pridgen to conclude that a virus must be involved.

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, lead 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 can  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’s been tried before in chronic fatigue syndrome, but not in the way Pridgen’s doing it.

connections

Are two ‘antivirals’ better than one? We’ll find out sometime next year.

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 IMC formulation used in the trial. It’s 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 antinflammatory (NSAID) COX-2 inhibitor usually used  in the treatment of osteoarthritisrheumatoid arthritisacute 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 won’t 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’s 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’ve 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’s 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 don’t 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.

stop sign

Pridgen believes Celexicob’s antiviral properties, in concert with Valtrex, will knock down the herpes viruses causing FM and 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’d 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 herpesviruses 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 herpesviruses particles themselves.

In preliminary studies 18/19 fibromyalgia patients with gut issues contained herpes simplex virus DNA in their gut tissues. No other herpesviruses were found. Immunoblot testing indicated that an active infection was present in eight of nine positive biopises.

Dr. Pridgen reported in an email they are still trying to determine  the optimum doses and cautioned everyone to wait until the results of the phase three 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 trial will be released mid-year, 2014. 

Conclusion

breakthrough arrow

A successful trial could usher in a new era of treatment for fibromyalgia and perhaps chronic fatigue syndrome

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 they results are positive, Pridgen and Duffy could usher in an entirely new way of treating both fibromyalgia and chronic fatigue syndrome.

Report From Paris: Peterson Reports Antiviral (Vistide) Effective in Treating Herpesvirus Infected Chronic Fatigue Syndrome (ME/CFS) Patients

PetersonPhoto right

“These results show objective endpoints, subset selection, and recovery. There were complete responders and partial responders among severely ill CFS patients with HHV6 or CMV. These are encouraging results for this subset and further well-designed trials should be pursued to confirm them.” Dr. Dan Peterson

At the HHV6 Conference in Paris, France today Dr. Peterson reported on the results of a retrospective study following 65 severely ill chronic fatigue syndrome patients given a course of Vistide from 2005-2012 for HHV6 and/or HCMV infections.  Despite the interest in pathogens in ME/CFS, antiviral studies are rare and this is the first one reported for this drug.

Virus from vistide presentation


Dr. Peterson has three decades of experience treating immunologically challenged ME/CFS patients.

Vistide (Cidofovir) gets a lot less press than other antivirals and immunomodulators (Ampligen, Rituximab, Valcyte,  Valtrex) used in this disorder  probably because the drug requires a  complex infusion protocol,  frequent blood tests because of the rare but real possibility of  serious kidney side effects and is expensive  (although it can be covered by insurance).

This combination – infusions, frequent blood tests and expense – requires close physician follow-up. With Dr. Peterson’s specialized focus on patients with dysfunctional natural killer cells, however, he may be most consistent about testing for herpesviruses, which are known to be active in ME/CFS patients.

After three decades of focusing on immunologically challenged ME/CFS patients, Peterson may be more experienced at pathogen detection and treatment than any other practitioner in the field, and so it’s not surprising to find the first Vistide study coming from his office.  In an interview, a former patient of his said, ‘he leaves no stones unturned’; when he finds something he goes after it ‘aggressively’.

In his presentation he stated  almost 30% of  his patients test positive for  active HHV-6 or human cytomegalovirus (HCMV) (PCR, rapid culture, antigenemia), and a whopping 50% test positive for active Epstein-Barr virus (EBNA) infection.

Serious Drug For A Serious Illness

Vistide (Cidofovir) is  FDA approved for the treatment of cytomegalovirus (CMV) in patients with AIDS. (Cytomegalovirus is a member of the herpesvirus family.) and it’s been used off-label to treat  human papillomavirus, BHK virus, herpes simplex virus, vaccinia virus infections. The Black Box warning on Vistide speaks for itself

 ‘Cases of acute renal failure resulting in dialysis and/or contributing to death have occurred with  few as one or two doses of Vistide. The “recommended dose, rate, frequency of Vistide injections must not be exceeded.”

The Study

A positive response was denoted by a negative pathogen test, improved fatigue and cognitive functioning determined by an interview with Dr. Peterson and  the patient’s self reports after the trial.

Response

  • Full Responders – Patients were deemed to be full responders if they were able to completely return to work or to work-related activities
  • Partial Responders – demonstrated significant improvement of symptoms but were unable to return to work or work related activities.
  • Non-Responders – Did not demonstrate any measurable improvement post-treatment

Results

Seventy percent patients improved

Seventy percent of ME/CFS patients with HHV6 and/or HCMV infections improved significantly on Vistide

Dr. Peterson reported that seventy percent of patients were full  (able to return to work) or partial (significant increase in functionality) responders; a very high rate of success in a illness characterized by a poor response to treatments.  Only thirty percent of Vistide recipients did not have a significantly positive response to the drug. No serious side effects were seen; ironically the minor side effects seen were attributed to a drug, Probocenid, used to ensure Vistide was safe.

It’s not clear what percentage of ME/CFS patients will test positive for HHV6 or cytomegalovirus in other practices but this type of response suggests the drug may be  being under-used. With the FDA Stakeholder’s meeting  coming up in three weeks and the Chronic Fatigue Initiative’s pathogen discovery study results due to be published later this year, Dr. Peterson’s presentation is timely. (Unfortunately, Dr. Peterson was not invited to present at the FDA Stakeholder’s Meeting.)

Dr. Peterson called for placebo-controlled, double-blinded multi-center studies that address Vistide’s efficacy, examine its effects on the immune system and study the mechanisms of increase in VO2 max scores in ME/CFS.

Sample Cases

Dr. Peterson reported on several cases, all of whom were men – something Dr. Peterson has said he likes to do to break up the notion that only women get this disorder.

  • A 27 year old college graduate  unable to work because of  constant flu-like symptoms, weakness and marked cognitive decline (math!) presented with low NK functioning, low VO2 max and HHV6 and cytomegalovirus infection. He was able to return to work after 24 weeks of bi-weekly infusions. His VO2 max on the exercise test went up went up 23%,  his NK cells a remarkable 400% and he tested negative for both viruses at the end of treatment. He had had ME/CFS for three years.
  • A 54 year-old former high school teacher unable to work due to extreme fatigue, flu-like symptoms and cognitive problems severe enough to keep him from being able to grade his students papers presented with active HHV6 and cytomegalovirus infections and low NK cell functioning and VO2 max. He was able to return to work after 24 weeks of bi-weekly infusions. His VO2 max increased 47%, his NK function test went up 20% and he tested negative for both viruses. He had had ME/CFS for five years.
  • The third patient had classic, acute onset ME/CFS which progressed to seizures. Both serum and cerebral spinal fluid tested positive for HHV6. At the end of the Cifodovir trial the  viral load in his cerebral spinal fluid dropped from 3670 copies/ml to undetectable levels. Serum HHV6 was dramatically reduced (47,000 copies/ml to 3,000 copies/ml). Still symptomatic and experiencing cognitive problems, he was nonetheless able to return to work.

Conclusions

The retrospective study indicated Vistide (cifodovir) can have dramatic effects on functional capacity in HHV6 and/or HCMV infected ME/CFS patients.

Increasing VO2 max appeared to be critical to increasing functionality as the partial responders did not increase their VO2 max while on Cifodovir. At the FDA Advisory Meeting for Ampligen Dr. Bateman noted that VO2 max test results probably were, given the exertional problems in ME/CFS, the most difficult to ‘move’ test result in this disorder.

VO2 max levels in Dr. Peterson’s patients prior to Vistide administration were exceedingly low; they appeared to in the ‘very low’ range even for people for 65 years of age and older. Vistide moved those test results about 20% on average; leaving them still, it appeared, below normal but sufficient enough for a significant increase in functionality.

A Vistide Example

Vistide_CFSThe VO2 max tests suggested most patients had not returned to full health and Dr. Peterson has said he knows of few complete recoveries. I interviewed a former patient of Dr. Peterson’s several years ago. Faced with the loss of his career and the ability to care financially for his family Vistide turned out to be a godsend.

Cut down by acute onset ME/CFS, his VO2 max score topped out at an unbelievably low 15 (which qualified him for heart disease) and he was a ‘2’ out of 10 on his own energy scale (had trouble sitting up to eat).  Within a month on Vistide he was at a ‘4’; the next month he was a ‘5’ and sleeping soundly for the first time since he’d gotten sick. The next month he was a ‘7’ and his VO2 max tests had doubled to 28; still far below the 44 expected at his age, but an amazing increase, never the less.  Three months later he was at ‘90%’, back at work and able to do everything except exercise.

CMX001 – The Future Vistide? 

Dr. Peterson didn’t report on CMX001 in Paris, but sitting in the background of all this is a analogue of Vistide called CMX001 which appears to be a safer and more effective,  if not yet available, version of it. A  2012 review named CMX001 as one the ‘ten hot topics’ in antiviral research.

Chimerix Pharmaceuticals modified Vistide so that it can easily be taken up into the  tissues. That means no need for infusions, no worries about kidney problem and according to Chimerix, dramatically increased effectiveness.

CMX001 has been in development for  some time but just this March the FDA awarded the drug ‘fast track’ status for the prevention of cytomegalovirus infection.  Phase II trials are finished  and Phase III trials will get underway this year.

Given Dr. Peterson’s success with Vistide, FDA approval of CMX001 could be very good news for ME/CFS patients with HHV6, HCMV and/or possibly EBV infections.

Wrap Up

In a retrospective study Vistide proved to be  effective  in treating severely ill ME/CFS patients with HHV6 and HCMV infections. Dr. Peterson called for double-blinded, placebo-controlled studies to further study Vistide’s efficacy and mechanism of effect.  The CFI’s pathogen discovery studies due out this year should shed light on what percentage of ME/CFS patients could benefit from Vistide.

A Vistide analogue under development called CMX001 which does not require infusions and does not effect the kidneys could be boon for ME/CFS patients with herpesvirus infections if it is approved by the FDA. CMX001 was given fast-track status by the FDA earlier this year.

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