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.
Testing - For more information on
Testing click here
"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. Check out more on
her XMRV Lecture
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".
Dig Deeper: Other ME/CFS Physicians on
Fatty Acids
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.
The Phoenix Rising website is compiled by a layman. It is not a substitute for a
physician and is for informational uses only. It does not present complete
information on this drug. Please discuss any treatments in these pages with your
physician.