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Novel Approach to Herpesvirus Infections Could Reap Dividends for Chronic Fatigue Syndrome Patients

Liang Y, Vogel JL, Arbuckle JH, Rai G, Jadhav A, Simeonov A, Maloney DJ, Kristie TM. Targeting the JMJD2 Histone Demethylases to Epigenetically Control Herpesvirus Infection and Reactivation from Latency. Sci Transl Med. 2013 Jan 9. PMID: 23303604.

Common Infections..Sometimes Uncommon Effects

An uncommon common virus

Unlike most viruses once you’re infected with herpesviruses you’re usually infected for life.

Herpesviruses are fundamentally different from most other viruses we come into contact with.  Most viruses  get completely eliminated from our systems  but herpesviruses have found a way to stick around – usually effectively bottled up by our immune system – for a lifetime ride in our cells. Very common in humans, we’ve all been exposed to and almost all of us carry a  latent or inactive herpesvirus infection.

Usually contracted in childhood most herpesvirus infections produce nothing more troubling than a childhood cold but they have a dark side.   A Epstein Barr virus infection that causes a mild cold in childhood often produces  infectious mononucleosis in adolescents and increase one’s risk of later coming down with multiple sclerosis and ME/CFS.  A mild herpes simplex infection during childhood can turn into an  painful case of shingles when we’re older.

Herpesvirus infections may be ubiquitous and usually mild but they  can cause encephalitis, blindness, horrific neurological problems and inflammation if they hit the right person at the wrong time. Not surprisingly, people with impaired immune systems such transplant patients are at high risk of herpesvirus reactivation with sometimes deadly consequences.

Key Viruses in Chronic Fatigue Syndrome (ME/CFS)

herpesvirus

A significant percentage of people may have reactivated herpesvirus infection.

Herpesviruses may play a key role in ME/CFS as well. How many people with chronic fatigue syndrome have a reactivated form of the virus is still unclear but some doctors believe the percentage is substantial. Many people begin their experience with chronic fatigue syndrome (ME/CFS) with a herpesvirus infection in the form of infectious mononucleosis.

Dr. Lerner and Dr. Glaser believe an unusual form of Epstein-Barr  virus is wreaking havoc in many patients. Their model suggests proteins and enzymes produced by a  partial reactivation of the virus are sending  the immune system into a tizzy and causing fatigue and other symptoms. Because the current slate of  herpesvirus antivirals attack the virus in the later stages of it’s development they’re in effect missing the action in ME/CFS.  These drugs work to some degree.  As they slowly lower viral load, the cells harboring the viruses die off over time.

Help Needed 

“there remains a clear need to develop new antivirals”

The problem is that in this model  the road to recovery takes time and lots of it; often a year or more of taking expensive antivirals. Dr. Lerner’s  been looking for a treatment that will hit the virus just as it’s starting to replicate and he’s  not alone. Even when the full virus is present, the present slate of  antivirals still sometimes  arrive too late to prevent blindness, neurological problems, birth defects and inflammation. The current herpesvirus antivirals come too late to the scene to

  1.  block the production of mutant viruses that can give rise to resistant strains of virus
  2.  block the expression of early viral enzymes that effect  and can produce cancer in cells
  3.  block the product of viral proteins that can trigger a damaging immune response (Lerner/Glaser’s theory of ME/CFS)

A Possible Breakthrough

A new approach to treating herpesvirus infections could reap dividend for other viral infections as well. An entirely different way of treating herpesvirus infections could reap dividend for other viral infections as well.

A new approach to attacking hard to treat herpesvirus infections could reap dividend for other viral infections as well.

“Depletion of the JMJD2 members or inhibition of their activity with a new drug results in repression of expression of viral immediate early genes and abrogation of infection. This inhibitor also represses the reactivation of HSV from the latent state in sensory neurons”

That may be changing. Researchers working at National Chemical Genomic Center (NCGC) have a developed  a ‘probe’ that stops herpesviruses from replicating by  pouncing  on the early enzymes they use to build a new virus.   (Ironically the virus uses our genetic machinery to get our bodies to produce the enzymes to build another virus). These researchers were able to design this probe after they figured out what genes these herpesviruses activate early in their life cycle.  This ‘epigenetic’ approach – stopping a virus by targeting the genes it needs to replicate – may very well herald a new era in antiviral therapy.

It’s  death by small cuts. By continually stopping the virus from replicating the herpesvirus will eventually  die when the cell they’re  living in dies. The good news for ME/CFS patients is that this probe could also whack the very enzymes Lerner and Glaser believe are causing ME/CFS. That could  mean no more long, expensive and sometimes dangerous treatment regimens.

The Implications for Chronic Fatigue Syndrome (ME/CFS)

This study focused on two herpesvirus infections (cytomegalovirus (HCMV), herpes simplex) sometimes found in ME/CFS. In Dr. Peterson’s presentation in Paris on the successful treatment of HCMV infections in ME/CFS, he reported that a small subset of ME/CFS patients have an active herpes simplex infection, as did Dr. Montoya at the FDA Drug Development Workshop.

Epstein-Barr Virus and Human Herpesvirus 6?

 Continued elucidation of the mechanisms and components involved in epigenetic regulation of viral pathogens will lead to additional targets for antiviral development

Epstein-Barr Virus (EBV) and Human Herpesvirus 6 (HHV6) are the pathogens most commonly associated with ME/CFS, however. I was unable to determine if the  enzyme targeted by this probe is found in these viruses. The fact that the  herpesvirus family undergoes a process called chromatic assembly and modulation in which the enzyme plays a role  suggests the probe might be effective in other herpesviruses.The fact that the probe worked in both alpha and beta herpesviruses (EBYis a gamma herpesvirus) suggests it may have widespread application but we’ll have to see if it applies to these viruses as well.

Dr. Martin Lerner, a specialist in treating herpesvirus infections in chronic fatigue syndrome has high hope for this approach.

My own research suggest immediate early gene products initiate CFS.  I think this work has great promise in effectively inhibiting many herpesviruses. Dr. Martin Lerner

Even if it doesn’t this discovery provides a new approach to drug treatment  that could be duplicated in other herpesviruses. Indeed these researchers are already looking for other epigenetic targets, one of which is found in Epstein-Barr virus.

This ‘probe’ has still  long way to get to the marketplace. It’s demonstrated its effectiveness in cultured cells and now needs to be assessed in animal models and  humans.

outside the box

This same epigenetic approaches that are effective in cancer are effective with viruses as well.

A New Paradigm for Antiviral Drug Development

There is intensive focus on the development of inhibitors of epigenetic components for the treatment of cancers and other diseases. The study presented here demonstrates that epigenetic inhibitors can also function as antiviral therapeutic agents.

The success of a drug employing a epigenetic approach to infection was big news with the study appearing in the premier scientific journal Science and the authors urging other researchers to pour resources into developing more epigenetic tools to fight infection.

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17 Comments

  • Mary Jane

    June 8, 2013 at 7:30 pm - Reply

    brain fog here :( so whats the treatment?

    • Cort Johnson

      June 12, 2013 at 4:27 am - Reply

      Sorry about that. This drug (unnamed in the study) targets certain genes to stop replication of herpesviruses…

      “Depletion of the JMJD2 members or inhibition of their activity with a new drug results in repression of expression of viral immediate early genes and abrogation of infection. This inhibitor also represses the reactivation of HSV from the latent state in sensory neurons”

  • anna

    June 8, 2013 at 8:27 pm - Reply

    Just read about an herb that basically does similar thing. Choparral is the name. Its attacks the herpes virus way before the stage at which common antivirals attack it. I do believe herpes and its cousins have a lot to do w cfs.. so this is pretty exciting actually. Just sad that allopathic medical community is still searching for synthetic human made solutions and is not looking at what we already have.

  • Lisa

    June 8, 2013 at 10:13 pm - Reply

    I’ve had great success with Enzymedica’s Virastop

  • Carol

    June 9, 2013 at 1:02 pm - Reply

    Exciting news! Thanks, Cort.

  • nancy

    June 9, 2013 at 2:20 pm - Reply

    Did I miss it? Cort your article talk about a treatment without telling the treatment is? Please clarify the the actual treatment it. Thanks.

    • Cort Johnson

      June 9, 2013 at 2:38 pm - Reply

      Sorry guys for not being clear. This is a drug that targets certain genes to stop replication of herpesviruses…

      “Depletion of the JMJD2 members or inhibition of their activity with a new drug results in repression of expression of viral immediate early genes and abrogation of infection. This inhibitor also represses the reactivation of HSV from the latent state in sensory neurons”

      I’ll get this in the blog…

    • Cort Johnson

      June 9, 2013 at 2:39 pm - Reply

      Sorry about that. This drug (unnamed in the study) targets certain genes to stop replication of herpesviruses…

      “Depletion of the JMJD2 members or inhibition of their activity with a new drug results in repression of expression of viral immediate early genes and abrogation of infection. This inhibitor also represses the reactivation of HSV from the latent state in sensory neurons”

  • Geraldine O'Sullivan-Hogan

    June 10, 2013 at 10:10 pm - Reply

    Chaparral

    Other common name(s): greasewood, creosote bush, jarilla, hediondilla, gobernadora

    Scientific/medical name(s): Larrea divaricata coville, Larrea tridentata (DC) coville

    Description

    Chaparral is an herb that comes from the leaves of the creosote bush, an evergreen desert shrub. The term “chaparral” refers to a group of plants dominated by evergreen shrubs that have small, stiff leaves. They grow in dense clusters to heights of 4 to 8 feet in the American West and Southwest, as well as in parts of Mexico and South America.

    Overview

    Chaparral is considered a dangerous herb that can cause irreversible, life-threatening liver damage and kidney damage. The U.S. Food and Drug Administration (FDA) has cautioned against the internal use of chaparral. Research has not found it to be an effective treatment for cancer or any other disease.

    A clinical study of nordihydroguaiaretic acid (NDGA), one of the chemicals in chaparral, concluded that it was not useful in treating people with cancer, although research continues.

    How is it promoted for use?

    Proponents claim that chaparral can help relieve pain, reduce inflammation, aid congestion, increase urine elimination, and slow the aging process. It is also promoted as an anti-cancer agent and an antioxidant (a compound that blocks the action of free radicals, activated oxygen molecules that can damage cells). Some promoters call it a “cleanser” or detox herb.

    Some researchers think NDGA might make other anti-cancer drugs more effective, but this theory still needs to be tested with clinical trials in people who are getting cancer treatment.

    What does it involve?

    Chaparral is sold in capsule, liquid, powder, or tablet form. Chaparral also can be made into a bitter and unpleasant-tasting tea or a tincture, a solution of chemicals from chaparral leaves dissolved in alcohol. Chaparral is also sometimes found with other herbs in “anti-cancer tea”.

    What is the history behind it?

    Native Americans used chaparral as an herbal remedy. They heated the leaves and applied them to the skin to treat wounds, bronchitis, coughs skin disorders, venereal sores, warts, blemishes, and ringworm. Heated stems were inserted into tooth cavities to relieve pain, and the leaves and stems were boiled to make tea to relieve rheumatism and other conditions, including colds, bronchitis, digestive problems, and cancer.

    According to individual reports, chaparral tea was used widely in the United States from the late 1950s to the 1970s as an alternative anti-cancer agent. Experimental studies in the 1960s showed that chaparral could cause problems with kidney and liver function. Because of this, the FDA removed nordihydroguaiaretic acid (NDGA) from its “Generally recognized as sate” list.

    The growth of interest in alternative medicine led to increased use of chaparral in the 1980s. By the early 1990s, there had been many reports of chaparral-linked illnesses, and the FDA issued a warning. This resulted in sellers voluntarily removing many chaparral products from stores. Despite many concerns and warnings, chaparral has become available again, and is advertised and sold from Internet sites.

    What is the evidence?

    Available scientific evidence does not support the idea that chaparral can prevent or slow the growth of cancer in humans, nor does it support chaparral as effective in treating other medical conditions.

    In 1970, researchers from the University of Utah published results of a clinical study sponsored by the National Cancer Institute on chaparral tea and NDGA. People with advanced, incurable cancer drank chaparral tea or took doses of pure NDGA by mouth. Of the 45 people who were evaluated, only 4 had a small decrease in the size of their tumors. These regressions lasted between 10 days and 20 months. But in others treated with chaparral, the tumors grew larger. The authors concluded that chaparral tea was not an effective anti-cancer agent.

    Some studies in the lab have suggested NDGA may possess anti-cancer properties. But studies of NDGA have had conflicting results. According to a 1990 government report, some researchers reported that NDGA inhibited cancer growth in animals. Others found that low levels of NDGA actually stimulated the growth of some types of tumor cells, although higher concentrations had the opposite effect. More recent cell culture studies using cancer cells grown in the lab suggest NDGA may make other anti-cancer drugs work better, and researchers are still looking into the potential uses of purified NDGA. While these studies show some promise, clinical studies are needed to find out whether NDGA may help people with cancer.

    More recently, a new chemical has been made from NDGA. It is called terameprocol (EM-1421), and is being studied as a cancer treatment, but is still in the early stages of laboratory testing.

    Are there any possible problems or complications?

    This substance may not have been thoroughly tested to find out how it interacts with medicines, foods, herbs, or supplements. Even though some reports of interactions and harmful effects may be published, full studies of interactions and effects are not often available. Because of these limitations, any information on ill effects and interactions below should be considered incomplete.

    Although chaparral is still widely available, the FDA has recommended since 1968 that it not be swallowed or taken internally by any other route. Chaparral can be highly toxic and has been reported to cause severe and permanent liver disease that can be fatal. It has also been linked to kidney damage, including cysts in the kidney and kidney failure.

    One case study reported that severe hepatitis developed in a 60-year-old woman who had taken chaparral for 10 months. She eventually required a liver transplant. In a later review of 18 case reports of adverse reactions associated with taking chaparral, researchers concluded that the herb is linked with irreversible liver damage and liver failure. Since these warnings were published, there have been fewer cases of liver damage reported.

    Chaparral may cause dangerous interactions with a number of other medicines and herbs. Blood-thinning medications (anticoagulants); non-steroidal anti-inflammatory medicines (pain medicines such as aspirin, ibuprofen, naproxen, and others); diabetic drugs; and certain antidepressants (MAO inhibitors) are thought to be likely to cause problems while taking chaparral. Always tell your doctor and pharmacist about any herbs you are taking.

    Other side effects of chaparral can include fatigue, stomach pain, diarrhea, weight loss, fever, itching, rash, and allergic reactions. This herb should be avoided, especially by women who are pregnant or breast-feeding.

    Relying on this type of treatment alone and avoiding or delaying conventional medical care for cancer may have serious health consequences.

    To learn more

    More information from your American Cancer Society

    The following information on complementary and alternative therapies may also be helpful to you. These materials may be found on our Web site (www.cancer.org) or ordered from our toll-free number (1-800-227-2345).

    Guidelines for Using Complementary and Alternative Therapies

    Dietary Supplements: How to Know What Is Safe

    The ACS Operational Statement on Complementary and Alternative Methods of Cancer Management

    Complementary and Alternative Methods for Cancer Management

    Placebo Effect

    Learning About New Ways to Treat Cancer

    Learning About New Ways to Prevent Cancer

    References

    Ding XZ, Kuszynski CA, El-Metwally TH, Adrian TE. Lipoxygenase inhibition induced apoptosis, morphological changes, and carbonic anhydrase expression in human pancreatic cancer cells. Biochem Biophys Res Commun. 1999;266:392-399.

    Fetrow CW, Avila JR. Professional’s Handbook of Complementary & Alternative Medicines. Philadelphia, PA: Lippincott Williams & Wilkins; 2004.

    Gordon DW, Rosenthal G, Hart J, Sirota R, Baker AL. Chaparral ingestion. The broadening spectrum of liver injury caused by herbal medications. JAMA. 1995;273:489-490.

    Kauma H, Koskela R, Mäkisalo H, et al. Toxic acute hepatitis and hepatic fibrosis after consumption of chaparral tablets. Scand J Gastroenterol. 2004 Nov;39(11):1168-1171.

    Medline Plus Web site. Chaparral (Larrea tridentata (DC) Coville, Larrea divaricata Cav) & Nordihydroguaiaretic acid (NDGA). Accessed at http://www.nlm.nih.gov/medlineplus/druginfo/natural/patient-chaparral.html on April 12, 2007. Content no longer available.

    Memorial Sloan-Kettering Cancer Center Chaparral. Accessed at http://www.mskcc.org/mskcc/html/69175.cfm on April 14, 2011.

    M.D. Anderson Cancer Center. Complementary/Integrative Medicine Education Resources, chaparral (larrea tridentata (dc) coville, larrea divaricata (cav) & nordihydroguaiaretic acid (ndga). Accessed at http://www.mdanderson.org/departments/cimer/display.cfm?id=5A5EF4F0-CF19-4FD1-9B40FD8546A616D9&method=displayFull on June 4, 2008. Content no longer available.

    Sheikh NM, Philen RM, Love LA. Chaparral-associated hepatotoxicity. Arch Intern Med. 1997;157:913-919.

    Smart CR, Hogle HH, Vogel H, Broom AD, Bartholomew D. Clinical experience with nordihydroguaiaretic acid — “chaparrel tea” in the treatment of cancer. Rocky Mt Med J. 1970;67:39-43.

    Soriano AF, Helfrich B, Chan DC, Heasley LE, Bunn PA Jr, Chou TC. Synergistic effects of new chemopreventive agents and conventional cytotoxic agents against human lung cancer cell lines. Cancer Res. 1999;59:6178-6184.

    Sun Y, Giacalone NJ, Lu B. Terameprocol (tetra-O-methyl nordihydroguaiaretic acid), an inhibitor of Sp1-mediated survivin transcription, induces radiosensitization in non-small cell lung carcinoma. J Thorac Oncol. 2011 Jan;6(1):8-14.

    US Congress, Office of Technology Assessment. Unconventional Cancer Treatments: OTA-H-405. Washington, DC: US Government Printing Office; 1990.

    Vickers A. Alternative Cancer Cures: “Unproven” or “Disproven”? CA: A Cancer Journal for Clinicians Volume 54, Issue 2, pages 110–118, March/April 2004

    Note: This information may not cover all possible claims, uses, actions, precautions, side effects or interactions. It is not intended as medical advice, and should not be relied upon as a substitute for consultation with your doctor, who is familiar with your medical situation.

    Last Medical Review: 08/16/2011
    Last Revised: 08/16/2011

  • Diana S.

    June 11, 2013 at 12:34 am - Reply

    I bet it will be along time before we see an FDA approved drug coming out of this study.

    • Cort Johnson

      June 12, 2013 at 3:55 am - Reply

      It may be…they’re just at the beginning of the process but this new approach got alot of publicity and there is a real need for better antivirals. Hopefully when they get to the human trials stage the FDA will put them on fast-track status and it will move along. It does take time, though – no doubt about it. CMX001 – another anti-herpes drug will surely come along more quickly. Chimerix recently went public and that drug is in its last trials, I think….

  • Susan S.

    June 12, 2013 at 3:51 am - Reply

    I’d love to donate $, but living on SSDI, that’s out of the question. I have both EBV and HHV-6, so if they need blood or tissue samples, I’m all theis.

    • Cort Johnson

      June 12, 2013 at 3:52 am - Reply

      Thanks Susan! You give what you can and blood and tissue is pretty darn good. :) . I’ll pass the word along.

  • Sarah Robinson

    June 12, 2013 at 7:08 pm - Reply

    Ms. O’Sullivan-Hogan, are you saying you know the probe or agent that was used in the NGCG study that Cort reported on? And that the “probe” the researchers were using was some version of Chaparral? I’d be very interested in what your lengthy explanation about Chaparral has to do with the prior article. (I do miss a lot of connections, so if the connection is obvious, please forgive me and fill me in.) Thanks!

  • Barbara Harman

    August 18, 2013 at 1:09 am - Reply

    I’ve noticed that whenever I get a herpes outbreak my dominant symptom, before any sore appears, is overwhelming fatigue. Until doing a Google search today (because I’m showing symptoms of a herpes outbreak) and coming up with this particular site, I had no idea there was any correlation between herpes viral infection and chronic fatigue and fibromyalgia. Presumably this is new research. I was diagnosed with fibromyalgia and chronic fatigue syndrome in 1996. I can’t really tell from what has been written whether this is research that is now in common medial knowledge or whether this is pretty new. I’ve never been tested (and didn’t know one could be) for any herpes viral load. The sore that I get (always in one of two places, the center of my lower lip or my left nostril) is usually minor. The fatigue, one other hand, is debilitating until the sore emerges.

  • lisa stallings

    January 10, 2014 at 11:20 pm - Reply

    I am taking Valtrex (old school anti viral) for massive brain fog- almost lost my life to hopefully herpes brain infection. Many people swear they see a profound difference in me I am still so sick that I need to get way better…

  • Gloria

    May 13, 2014 at 2:54 pm - Reply

    I was trying to find out if taking an enzyme supplement can bring on an outbreak of genital herpes

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