XMRV Treatment

Treating Chronic Fatigue Syndrome (ME/CFS): XMRV

“The scientific evidence that a retrovirus is implicated in CFS opens a new world of possibilities for so many people. Scientists can now begin the important work of translating this discovery into medical care for individuals with XMRV related diseases.” Annette Whittemore

At the Reno Conference Annette Whittemore evoked the possibility that the Institute was on the road to uncovering unusual drugs that would prove helpful and indeed the Institutes uncovery of similar immune system dysfunctions in ME/CFS patients and cancer patients opened the door to anti-cancer drugs. Now the discovery of a retrovirus opens the door to anti-retroviral drugs.

“Because we have so many FDA approved antiretrovirals particularly non-nucleoside RT inhibitors and integrase inhibitors as well as non -steroidal anti-inflammatories. We see great promise of combination therapeutic strategies very quickly.” Dr. Judy Mikovits

Treatment  – Dr. Mikovits stated that she “can imagine a number of combination therapies that could be quite effective and could at least be used in clinical trials right away”. She included AIDS drugs such as reverse transcriptase inhibitors and integrase inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs) and cancer fighting proteasome inhibitors. Dr. Klimas, an AID’s and ME/CFS researcher and physician stated that “The good news is that if XMRV is linked to C.F.S., there are many antiviral drugs that have already been safety tested in H.I.V. that may inhibit viral replication.” The WPI will be assessing the effectiveness of different drug therapies in some ME/CFS patients.

Dr. LeGrice of HIV/AIDS and Cancer Virology at the NIH stated that despite its retroviral roots XMRV is different enough from HIV that  he believes new kinds of drug will be needed. He stated, however, that “we’ve learned a lot from HV, and if XMRV does become a serious issue we can bring that to bear very quickly”.

“The good news is that if XMRV is linked to C.F.S. there are many antiviral drugs that have already been safety tested in H.I.V. that may inhibit viral replication.” Dr. Nancy Klimas

The WPI has displayed considerable optimism regarding the creation of new drugs to treat this infection. Dr. Bell stated also stated that XMRV “conceivably could be very treatable. Theoretically much more treatable than HIV”. One wonders if their optimism derives from the fact that the XMRV virus is much more primitive than the HIV retroviruses.

Dig Deeper! One of Dr. Peterson’s patients recounts his recent meeting with the Doctor

Note, though, that while the typical course of my anti-retrovirals in AIDS rapidly results in reduced viral loads and increased immune functioning that symptom remission can take far longer to achieve. Interestingly, the same is often true with the current antiviral regimes in ME/CFS; improved laboratory results can often be seen  quite rapidly but it takes a quite sustained  course of antivirals (>1 year) for symptoms to improved markedly. Note as well that it’s not currently possible to completely kill off a retroviral infection in the body. The goal is to inhibit it enough for people to be able to lead ordinary lives.

“If an individual gets the immune system modulated to control and silence the virus then one can be well. The goal is to keep the virus quiet…There are two GRE sites in the CIA acting elements of the virus. These respond to hormones and cortisol.” Dr. Judy Mikovits

THE DRUGS

When Dr. Mikovits talked about AIDS drugs she was referring to a substantial number of drugs. Roughly 30 drugs have been approved for AIDS with about ten more going through drug trials. Dr. Klimas reported that drug companies have literally thousands of compounds sitting on their shelves that didn’t make it to the HIV market but could work for XMRV.

Retroviruses are pieces of RNA that enter a cell, turn their RNA into DNA, insert their DNA into the cells genome and then use the cells genome to produce more retroviruses. Each of the drugs devised to combat retroviruses seeks to block one of these steps.

Drug Trials. Two drug trials have examined drug efficacy against XMRV. The Feb 2010 Sakuma study – containing 10 anti-retroviral HIV drugs – found that none of the drugs stopped XMRV activity but that AZT blocked XMRV replication – thus preventing it from infecting other cells (Sakuma et. al. 2010) Thus, none of the drugs effected XMRV while it was in the cell but AZT stopped it from spreading and doing its mischief once it emerged from the cell.

A March, 2010 Singh study noted that few antiretroviral agents have been tested against XMRV-like viruses and that the protein structures of HIV and XMRV differ so much that it’s difficult to predict which HIV targeted drugs might work for XMRV. Dr. Singh took several drugs from each class of the known antiretroviral drugs plus some that are still in the development stage as well as some antivirals, put them into cultures of XMRV and then determined if they were able to inhibit virus.

Of the 45 compounds tested four ‘strongly inhibited’ XMRV in cell cultures: RAL, L-000870812, ZDV and TF. Because low doses of these compounds were sufficient to significantly inhibit XMRV, Dr. Singh suggested patients might be able to tolerate them well. The fact that combining the drugs together enhanced their effectiveness suggested that ‘drug cocktails’ (aka AIDS) might be a possibility.  In contrast to the Sakuma study, Raltegavir worked effectively in four different types of cells. The results of these laboratory studies may or may apply to the more complicated situation in the body

Individual Drugs

Raltegavir (TF) – is the first of a new class of anti-retroviral drugs called ‘integrase inhibitors’, Raltegavir was approved to treat retroviral infections in October 2007. Integrase inhibitors attack retroviruses after they have entered a cell and prevent them from inserting their genetic material into the DNA of the cell. Because retroviruses replicate by inserting their genetic material into a cells DNA, integrase inhibitors could stop retroviral replication. Because XMRV’s possibly tumor causing effects are believed to result from it’s propensity to insert itself near ‘oncogenes’, Raltegavir could block this process as well. Timothy Luckett proposed that Raltegravir might be the best candidate for XMRV treatment in his blog.

  • Side effects – the most commonly reported  side effects are diarrhea, nausea and headache. Blood tests showed abnormally elevated levels of a muscle enzyme—creatine kinase—in some patients. Isentress should be used with caution by patients who are at an increased risk of muscle problems like myopathy and rhabdomyolysis.

AZT  – AZT was originally developed in the 1960’s as an anticancer drug. The first drug to be approved for the treatment of AIDS in the mid 1980’s, AZT inhibits retroviral replication by preventing the virus from transcribing it’s RNA into DNA. Because AZT does not kill retroviruses it can only delay progression of the disease. HIV was eventually able to mutate and become AZT resistant and AZT is now used only in combination with other classes of drugs.

 

  • Side Effects: common side effects include nausea, headache, changes in body fat and discoloration of the toe and fingernails. More serious side effects include anemia, neutropenia (low white blood cell counts) and bone marrow suppression. AZT can also damage heart and other muscles because it has a high affinity for DNA polymerases in the mitochondria. Very rarely it can cause pancreatitis, vasculitis and seizures. Most physicians do not recommend a trial course of AZT.
  • ME/CFS and AZT – Dr. Peterson has reportedly been open to AZT trials in some patients. Citing the potentially very serious side effects, Dr. Mikovits has not. Some ME/CFS patients are trying AZT. Anecdotal reports suggest that a few patients have improved and others have not. Follow the discussion on AZT and ZMRV and a patients experience on the drug on the XMRV Treatment section of the Phoenix Rising Forums.

Ampligen   – Dr. Peterson has found that in the lab at Ampligen reduces viral load in some patients and not in others. For more on Ampligen

A Genetically Homogenous Virus AIDS Treatment Efforts Dr Singh noted how genetically homogeneous XMRV appears to be; the most distinct strains collected from distant parts of the US thus far have differed in only 27 out of 8,100 nucleotides (!). This could be helpful for XMRV infected patients because it suggests that XMRV replicates very slowly. If the virus is staying ‘static’ then it’s not evolving to escape the effects of whatever drugs are thrown at. This suggests that the possibility of drug resistance to XMRV is probably much lower than for HIV and that the ‘drug cocktails’ manufactured for virus might be simpler.

Anti-Herpes Drugs Do Not Work – Several anti-herpes virus drugs (Foscarnet, Ribivarin, Acyclovir, Ganciclovir, Vistide) were found not to be effective against XMRV. It’s unfortunate that she did not test some of the herpesvirus drugs more commonly used in CFS (Gangciclovir, Valaciclovir (Valtrex), valganciclovir (Valcyte)). However, the finding that Vistide was not effective against XMRV, suggests that that XMRV may not be a major factor in those patients who improved dramatically on Vistide.

PATIENT REPORTS

Several people are reporting on their trials with antiretroviral drugs.

PHYSICIAN REPORTS

 

Dr. Klimas – recommends that patients pretty much follow their standard protocol. She highlighted isoprinosine (inosine), COQ10, omega 3 fatty acids, a good multiple vitamin with B-complex, the sleep drug Xyrem and very short periods of exercise.

Dr. Cheney’s Approach   – Dr. Cheney is the only physician I am aware of who has something of an anti-retroviral treatment protocol laid out (Note that it resembles his standard treatment protocol.) Dr. Cheney stated that shifting the ‘redox’ environment in the body to a less oxidized state (i.e. less free radicals) will be sufficient to break the bonds XMRV uses to attach to cells and hence stop it from replicating. He also posits that an oxidative charged environment – such as ME/CFS patients exhibit – results in increased XMRV replication.

He proposes that ME/CFS patients tend to stay away from known oxidizing agents (high meat diets, sugars, fructose, processed foods, allergic foods, fish oil in the special case of CFS, environmental exposures and especially mercury (Sushi), dirty amalgam extractions, cracked amalgams and immune activators such as vaccinations and echinacea, mold, stress or chaos in your life, heavy exercise, excessive heat or cold and EMF). (Note – Dr. Cheney is unusual among ME/CFS doctors in his dismissal of fish oil, reducing agents such as COQ10 and other substances. For more on Dr. Cheney’s new (and controversial) treatment approach and how he derived it check out the link below. )

Dig Deeper: “Dr. Cheney Goes His Own Way“.

Dr. Cheney also suggests that ME/CFS patients introduce ‘reducing factors’ such as fresh vegetables (preferably raw – especially freshly juiced green drinks), olive oil, low stress, clean environments, low EMF exposure (aka avoiding cell phones and unshielded house currents), and avoiding drugs that induce P450 enzyme. He states that probably the worst environment “is severe stress or life chaos combined with a bad diet and mercury exposure.”

Dr. Cheney’s main strike at the XMRV virus, though, will focus on herbal products called arteminisins (artesunate and wormwood) that are able to inhibit a central inflammatory factor called NF-KB. He will be testing the efficacy of artemisins against XMRV in his patients.

Dig Deeper! Artesunate and ME/CFS

Dr. Mikovits – Dr. Mikovits is a researcher not a physician. In her Prohealth talk in Jan she stressed that patients do their research and not take too many supplements but recommended anti-oxidative treatments (glutathione, NAC, etc.)and, because several hormones, including cortisol appear to trigger the XRMV activity, trying to reduce stress levels.

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