including a link to an interview with Laura Hillebrand, author of
Seabiscuit, by The New Yorker, the Oct. 29-30 CFSAC meeting agenda is
published, which is to include a presentation by Dr. Daniel Peterson
entitled 'XMRV Association with CFS', and CFIDS Assoc. Scientific
Director Suzanne Vernon writes about the new XMRV findings-
http://www.facebook.com/CFIDSAssn
------------------------
Oct. 29-30 CFSAC agenda-
http://www.hhs.gov/advcomcfs/meetings/agendas/cfsac091029_agenda.html
-------------------------
Interview w/ Laura Hillebrand-
(http://www.newyorker.com/online/blogs/backissues/2009/10/back-issues-laura=
-hillenbrand.html)
------------------------
Xplained
By Suzanne D. Vernon, PhD
Scientific Director, the CFIDS Association of America
http://www.facebook.com/note.php?note_id=3D185660730538&ref=3Dmf
The announcement on October 8, 2009, that an infectious retrovirus
called XMRV (xenotropic murine leukemia virus-related virus) was
linked to CFS, could be the game-changing scientific event we have
been waiting for. Whether XMRV provides the long-awaited causal link
will depend on the findings described in the Science paper being
replicated by another laboratory in another group of CFS patients. To
help clarify what we know, let=92s review the findings.
Dr. Judy Mikovits and her team at the Whittemore Peterson Institute
for Neuro-immune Disorders (WPI) made a very insightful connection
three years ago. XMRV was first described in prostate cancer in 2007
by investigators at the Cleveland Clinic, who also reported that
XMRV-positive prostate cancer patients have alterations in RNase L, an
antiviral immune system pathway. The WPI investigators knew that RNase
L activity is also altered in blood cells from CFS patients and they
made the decision to look for XMRV in CFS patients with this immune
defect.
When scientists want to find a virus, we look for it in the sickest
individuals because often this is where there is likely to be the
highest levels of a virus, if present. Dr. Dan Peterson has been
caring for and researching CFS patients since the 1984 Incline Village
outbreak, so he identified CFS patients with prolonged disabling
fatigue, cognitive impairment, and documented laboratory immunological
abnormalities (including altered RNase L activity) to hunt for XMRV.
The WPI laboratory team detected XMRV sequences in 68 of 101 (67%) CFS
patients tested and in 8 of 218 (3.7%) healthy control subjects. The
Cleveland Clinic confirmed the presence of XMRV in a subset of these
same CFS cases, 7 of the 11 samples from WPI. The Cleveland Clinic
researchers found that the CFS XMRV was similar to prostate cancer
XMRV, and not a mouse virus (murine leukemia virus) that could have
been a contaminant explaining the discovery.
The investigators designed several laboratory tests to understand
XMRV. They looked to see if XMRV was expressed in peripheral blood
mononuclear cells (PBMCs) of CFS patients. PBMCs circulate throughout
the entire system and can be important =93sentinels=94 for processes
occurring in the body. PBMCs from 19 of 30 CFS patients expressed XMRV
proteins compared to 0 of 16 PBMC samples from healthy controls. They
also wanted to know which cells harbored XMRV; they found it in T and
B cells in the blood of one CFS patient. The investigators looked to
see if the XMRV from CFS patients was infectious. Both blood cells and
plasma (the cell-free fraction of blood) from XMRV-positive CFS
patients were able to transmit this virus to a susceptible cell line,
indicating the virus could be transmitted in laboratory culture.
Finally, they wanted to know if XMRV stimulated the immune system to
produce antibodies. Plasma from 9 of 18 CFS patients had antibodies
that reacted with a virus protein similar to that found in XMRV,
compared to no reaction from plasma of 7 healthy controls.
This Science paper tells us that XMRV plays a possible role in CFS
pathogenesis in these CFS patients. How much we can generalize these
findings to other CFS patient populations? That answer will depend on
the results of replication studies.
The design of replication studies should include CFS patients who are
similar to those selected by Dr. Peterson and reported in the Science
study. Unfortunately, the details about the CFS patients were not
sufficient to enable independent investigators to select similar CFS
patients. For example, we need to know the age, sex, duration of
illness, medical history, and medication use =96 to name a few
characteristics =96 of the studied patients to select CFS patients who
are as similar as possible to the original group. We also need to know
something about the healthy control subjects, since there is nothing
in the paper or supplemental materials that describes how they were
selected. Independent replication studies should also include patients
with mild and moderate CFS, at least one chronic disease control group
(e.g., multiple sclerosis, lupus) and sex and age-matched healthy
controls. We are actively working with several independent research
groups to expedite these studies.
While these exciting studies of XMRV continue, the CFIDS Association
continues its support of our funded investigators. It=92s important to
remember that HIV was first linked to AIDS in 1983, yet worldwide
research on HIV continues today. Our funded investigators=92 research on
why Epstein-Barr virus (EBV) triggers CFS, whether ion-channel
receptors are markers of fatigue, why CFS patients have higher rates
of leaky gut, why CFS patients have slow blood flow to the brain, why
CFS patients have metabolic disturbances in the brain, and how we can
bring this information, as well as XMRV, together using powerful
computational tools are all important as we work together to solve
CFS.
References:
Detection of an infectious retrovirus, XMRV, in blood cells of
patients with chronic fatigue syndrome. Lombardi VC, Ruscetti FW,
Gupta JD, Pfost MA, Hagen KS, Peterson DL, Ruscetti SK, Bagni RK,
Petrow-Sadowski C, Gold B, Dean M, Silverman RH, Mikovits JA. Science
8 October 2009. 1179052.
Supporting online material for Detection of an infectious retrovirus,
XMRV, in blood cells of patients with chronic fatigue syndrome.
Lombardi VC, Ruscetti FW, Gupta JD, Pfost MA, Hagen KS, Peterson DL,
Ruscetti SK, Bagni RK, Petrow-Sadowski C, Gold B, Dean M, Silverman
RH, Mikovits JA. Science 8 October 2009.
A new virus for old diseases? Coffin JM and Stoye JP. Science 8 October 8 2=
009.
Information about the Association's research program:
http://www.cfids.org/about/acceleratecfsresearch.asp
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