Sunday, April 10, 2011

XMRV and Treatments

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Innovative Healthcare

3471 Regional Parkway
Santa Rosa, CA 95403


This Update on XMRV
is by Dr. AzRa Mael, MD:

What is XMRV (aka Xenotropic
Murine Leukemia Virus-Related
Virus)?  Does it cause Chronic
Fatigue Syndrome?  What other
illnesses might it be associated
with? How can it be treated?

XMRV is the current name given to this recently
discovered group of retroviruses that infects

It is a member of the third known family of human
retroviruses, a Human Gamma Retrovirus (HGRV),
and in time these viruses may be renamed HGRV.

Human Immunodeficiency Virus (HIV) and Human
T-Lymphotropic Virus (HTLV) are the other 2 families
of human retroviruses that  may be more familiar to

XMRV was first discovered in association with
prostate cancer in 1996. Only recently (2009) was
the virus found to be strongly associated with
Chronic Fatigue Syndrome by a group of collaborating
labs, including Dr. Mikovits's lab at the Whittemore
Peterson Institute (WPI).

The presence of other closely related  viruses
(murine leukemia virus related-viruses or MLV-related
viruses) was then independently and robustly
confirmed by the Harvard / NIH / FDA collaborative
effort headed by Dr.'s Lo and Alter in 2010.

The family of viruses consists of multiple closely
related viral mutations, which is typical of
retroviruses.  In studies, approximately 80-90%
(perhaps more) of people with CFS have XMRV and
closely related viruses, compared to 4-7% of

The strength of this association has led to the
hypothesis that XMRV causes CFS.

However, it is more complicated than that. In
unpublished studies from Dr. Paul Cheney and
Gordon Medical patients, approximately 40-50% of
healthy family members and close contacts of people
with CFS are infected with  XMRV.

XMRV alone  may not be sufficient to cause CFS in all
people, but it appears it may be a necessary
contributing factor, possibly in combination with
another undetected retrovirus, another infection, or a
genetic susceptibility to XMRV.

It is possible not everyone infected will develop
disease in response to XMRV. In the case of HTLV,
another human retrovirus, we see a similar pattern in
that only 10% of infected patients develop clinical

Since the original CFS paper published in Science
magazine in 2009, several research teams have
questioned the research of Mikovits, Lo, and Alter,
perhaps due to concern about the consequences of
the presence of XMRV in the nation's blood supply,
and the high cost of screening our blood banks.

A recent flurry of papers attempted to
debunk the XMRV research using the
issue of possible mouse DNA contamination.
The contamination concerns are generally
valid, but the research done by the group
for the Science paper, and the later paper
by Lo and Alter had already taken steps to
test for such contamination issues.

The contamination arguments, claiming the positive
results are due to mouse DNA, cannot explain why
positive samples show an immune response to
XMRV, or why XMRV can be cultured from samples.

In addition, the samples were tested specifically for
mouse DNA, in order to ensure there would be no

The contamination papers are not relavant to the
most important studies indicating the finding of
XMRV in Chronic Fatigue Syndrome, and the
existence of XRMV still stands firm.

As of December 2010, the American Red Cross and
international blood banks began banning blood
donation from people with CFS. The government is
currently working to develop a fast and accurate test
for XMRV in order to protect the blood supply.

In unpublished research XMRV has been found
associated with multiple other illnesses, including
chronic Lyme disease.

It is associated with lymphoma, prostate cancer,
inflammatory breast cancer, fibromyalgia, autism,
Parkinson's, and Multiple Sclerosis, among other
inflammatory conditions.

There is no proof yet that it is causative, but it is
being found in higher numbers than would otherwise
be expected.


XMRV Testing

Testing for XMRV has not proven easy. The Lo/Alter
paper has shown  there are many strains (mutations)
of XMRV and related MLV viruses (such as PMRV).

Different strains of the virus can only be detected
using the most sensitive PCR probes and under
exacting conditions, often requiring culturing of the
blood sample for several weeks to increase the viral
numbers to detectable levels.

Testing is also complicated by the fact that XMRV
can be undetectable in the blood, but may be found
instead in organs such as the spleen, lymph nodes,
and others.

Additionally, as in some other chronic infections, not
everyone who is infected with XMRV produces
antibodies, so tests that rely on measuring
antibodies can produce *false negative* results.

Patients who are negative by PCR, may be positive
by culture or serology/antibody, and vice versa.

Dr. Mikovits is currently working on a way to detect
more of the strains of the MLV viruses in the XMRV
family, as well as faster and more sensitive tests for
both antibody and DNA of the entire family of

Patients who have tested negative for
XMRV should realize that it is still
possible they are infected, but it was
not possible to find the infection in that
sample on that day. Retesting on another
day, or by another type of test, may give
different results.

Samples from Gordon Medical patients who
participated in the XMRV study through WPI are
being used to help in the development of these new

Dr. Mikovits is continuing to actively test any
negative samples to ensure that any infections are
found if evidence is present in the sample.

When viral evidence is found, WPI is sequencing the
genetics to discover whether it is in this new family
of retroviruses.

Dr. Mikovits stated that she expects to have a new,
commercially viable test available by June of 2011.


Treatment Possibilities
for the New Human

Are there treatments for XMRV?  Will they
help people with CFS, cancer, or other

This is the hot topic that is still under investigation.

Doctors at Gordon Medical, the Whittemore-Peterson
Institute, and a handful of other centers across the
world are actively looking at possibilities.

At the time of writing, we know of approximately 65
CFS patients with XMRV who have tried various
combinations of three anti-retroviral (ARV)
medications originally designed for HIV: tenofovir,
zidovudine and raltegravir.

Each drug has been proven to inhibit XMRV viral
replication in in vitro (test tube) studies, and they
are synergistic when any two drugs are combined.

Dr. Joseph Brewer is one of the primary clinicians
doing trials with these medications. Dr. Brewer and
other CFS doctors report that after 6 months of use,
approximately 20-30% of patients on ARV's have
noticed mild to moderate improvements.

Though these medications help some people, they
are clearly not a complete solution for CFS and

There is still a  lot to learn about what doses, what
combinations, and what supportive therapies might
make them more useful for more patients.

Gordon Medical doctors, along with
several other centers around the world
are now looking at working with
immunomodulating treatments such as
Gc-MAF, stem cells, Peptide T and others
that boost immune system function against
viruses and cancers.

Dr. Paul Cheney is one of the pioneers of umbilical
cord stem cells in the treatment of CFS and XMRV.

Based on 18 - 24 months of his experience with just
over 30 patients, it is clear that stem cells produce
dramatic improvements in most people under the age
of 36, moderate results in the 36 - 60 year age group
and mild improvements in those over 60 years of

Unfortunately, the good results are only temporary,
lasting approximately 6 - 18 months before patients
regress partially or completely.

Doctors at GMA are now investigating a technology
related to stem cells called Platelet Poor Particle
Rich Plasma that has proven beneficial to several
hundred patients, some with conditions related to
CFS, and will hopefully will have longer lasting
effects than umbilical cord stem cells.

Another promising immune therapy
is Gc-MAF (Gc protein-Macrophage
Activating Factor).

Gc-MAF activates macrophages, which
are immune system cells that are
important in eliminating infection and

Unfortunately, many cancers and viruses cause the
secretion of an enzyme called nagalase that digests
naturally occurring MAF in our bodies.

Gc-MAF has a similar effect to that of our naturally
occurring MAF, but Gc-MAF is not degraded by

Administration of Gc-MAF via intra-muscular injection
results in the reactivation of previously suppressed

Gc-MAF was first used by Dr. Yamamoto in the
treatment of HIV and cancer. Recently,
approximately 80 XMRV positive CFS patients in
Belgium and the U.S. have received Gc-MAF with very
promising initial results.

Patients who are considering this therapy can be
tested for nagalase levels as well as vitamin D
receptor mutations, which may influence the outcome
of Gc-MAF treatment.

Dr. Mikovits warns that it may be important
to use an anti-viral strategy in addition to
immunologic treatments that could
potentially activate a reservoir in the body
to express more virus. In addition to ARV
pharmaceuticals, agents such as artesunate,
nexavir and others have antiviral and anti-
inflammatory properties that retard the
growth of viruses.

Other factors that studies show may inhibit XMRV
replication are restoring healthy glutathione levels,
reducing oxidative stress, reducing inflammation, and
normalizing methylation.

Few people realize that our body can naturally
silence viral infections, including retroviruses such as
HIV and XMRV, through methylating viral DNA.

Conversely, if viral DNA is not properly methylated,
viruses will continue to reproduce and grow in our

We know that almost everyone with
CFS has a methylation cycle abnormality
that can be improved by taking methylation
enhancing nutritional supplements.

The study that proved this concept was co-written by
GMA's very own Neil Nathan, MD. Most people with
CFS have mild to moderate improvement in
symptoms when on methylating factors.

Some very sensitive patients find that starting
methylation supplements can exacerbate symptoms,
so as with all treatments, it is important to do these
in close consultation with your physician.

Viruses replicate more quickly in environments of
oxidative stress and inflammation. They also grow
more easily in low-glutathione environments.

As an adaptive mechanism viruses actually cause
oxidative stress, inflammation, and low glutathione
levels in our bodies that favors their survival.

By replenishing glutathione levels and reducing
oxidative stress and inflammation, we may inhibit
viral growth.

Many natural compounds have
anti-inflammatory properties. One
group of compounds that has proven
to inhibit both the herpes viruses and
the NF-kB inflammatory pathway is
artesunate and related artemisinin

Dr. Mikovits and the doctors at Gordon Medical
believe it will be important to diagnose and treat
co-infections in patients infected with XMRV, just as
it is with HIV.

In the Gordon Medical cohort so far approximately
half of the patients who are positive for XMRV also
have Lyme disease. Many also have EBV, HHV-6 and
CMV, and other infections.

Some patients who are diagnosed with *CFS*
respond partially or completely after treating the
Lyme disease.

Other patients experience benefits by taking valtrex,
valcyte or other antiviral medications active against
herpes-viruses. Though valtrex and valcyte do not
usually cure CFS, they can help people feel better by
reducing the immune system load imparted by viral

Studies have shown that hormones
such as cortisol, testosterone and
estrogen can promote XMRV replication.

Each of these hormones performs critical functions in
our body, so some amount is needed, but in excess,
or out of balance, they may be harmful.

Cortisol is produced in response to stress, and
most people with CFS are familiar with how
stress impacts their symptoms.

Estrogen, progesterone, testosterone
and DHEA are often low or out-of-balance
in CFS. Some patients feel better on
low-level supplementation of these
hormones, but some worsen. It is
important to pay close attention how
one's body responds to hormonal shifts
in order to stay in balance.

The good news is that with every passing year, our
understanding of CFS is getting better and better.
Though CFS is still a challenging illness to treat,
recently discovered treatments have resulted in
marked improvements in a growing percentage of
patients with CFS, which represents a significant
advance compared to years past.

It is important to remember
that each of the therapies
mentioned in this newsletter
are experimental.

There are no published
clinical trials yet, only informal
observations made by groups
of astute doctors and patients.

The practitioners and staff at GMA thank you for your
time and interest.We will continue to collaborate
with the Whittemore-Peterson Institute and share
the latest advances in CFS and XMRV research.

We would also like to extend our appreciation and
gratitude to the courageous patients dealing with
CFS, XMRV, chronic Lyme disease and related
illnesses who have maintained hope, raised
awareness and pushed us forward.

Dr. AzRa MaEl, MD

If you have questions about XMRV, the lecture, or
our studies, please contact:

Susan Friedl
Research Coordinator
Gordon Medical Associates


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