XMRV -Seeking New Blood-Supply Test

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THE WALL STREET JOURNAL

* NOVEMBER 23, 2010

Seeking New Blood-Supply Test

By AMY DOCKSER MARCUS

Scientists are racing to develop tests for a retrovirus called

XMRV, which could be used to determine if the blood supply

is tainted and to assess how many people may be infected.

The impetus behind the drive is a paper published in the

journal Science last year that reported a link between XMRV

and chronic fatigue syndrome.

Public health officials were alarmed that close to 4% of

healthy people used as controls in the study were infected

with XMRV. That could mean as many as 10 million Americans

are infected.

XMRV has gotten a lot of attention because, like HIV, it is a

retrovirus. This means the virus cannot be eradicated from the

body, only controlled.

There is some preliminary evidence that XMRV may be

transmitted sexually or through transfusions. While the

retrovirus has been linked to certain diseases, scientists

don't yet know if it actually causes any disease.

The virus doesn't appear to replicate as frequently as HIV,

making it challenging to detect. How labs handle blood

samples before they test for XMRV may have an impact on

results, some researchers believe.

Some labs haven't been able to find it in people with chronic

fatigue syndrome or prostate cancer, which have both been

linked to the retrovirus.

There has also been debate over the criteria used to define

patients with chronic fatigue syndrome.

These issues have made it challenging to come to a consensus

on how many people are actually infected and whether or not

XMRV poses a health risk.

Tests are in the works at a number of labs, including the

Centers for Disease Control and Prevention and the National

Cancer Institute as well as Abbott Diagnostics, a division of

Abbott Laboratories, and Gen-Probe Inc. Roche Diagnostics

says it expects to have a test for research purposes ready in

months.

Busch, director of the Blood Systems Research

Institute in San Francisco and a member of a federally funded

blood-working group studying the potential impact on the

blood supply, says the group pushed for companies to get

involved early on in developing XMRV tests because they have

technology that allows them to screen thousands of samples

quickly.

This kind of capacity " is critical to support our research studies

and resolve the questions about XMRV, " Dr. Busch says.

Various labs have their own tests but not everyone has been

able to find XMRV in patients. If it turns out that XMRV is

associated with diseases, there will be a need to screen large

numbers of people and fast, reliable methods to test for it.

A key challenge is that these are still early days in

understanding XMRV. Researchers usually calibrate tests

against clinical samples that everyone agrees are positive and

negative for the virus. A successful test would correctly

determine which samples are infected.

In the case of XMRV, there isn't yet scientific consensus. Some

labs have said they cannot find XMRV in blood samples from

patients that other labs have deemed positive.

To get around that problem, researchers at Abbott, Cleveland

Clinic and Emory University created their own positive samples

by using blood from monkeys that were infected with XMRV in

the lab. " There is always doubt about human samples, but

there are no ifs, ands, or buts about the animals being

infected, " says Silverman of Cleveland Clinic, whose lab

is working with Abbott and receives research funding from the

company.

Dr. Silverman also could receive royalty payments from Abbott

because of XMRV patents licensed to the company.

Researchers from the three institutions developed tests that

identify antibodies to three key proteins of XMRV, or

xenotropic murine leukemia virus-related virus. The presence

of antibodies indicates exposure to the virus.

Walter Kierans of Abbott Diagnostics says they were able

to find virus in the blood of the rhesus macaque monkeys

immediately after being infected, but that amount was

virtually undetectable in the blood within a few weeks.

This could provide one explanation for why it has been

hard for some labs to find the virus in the blood of patients.

Low levels of virus doesn't mean that XMRV isn't harmful,

Dr. Kierans said. Another retrovirus, HTLV, is also found in

low levels in the blood but causes leukemia in some infected

people.

Bagni, a scientist with a government contractor working

with the NCI, developed an XMRV antibody test using blood

from patients with chronic fatigue syndrome provided by the

Whittemore- Institute in Reno, Nev., whose

researchers led the team that published the Science paper.

For healthy controls, Dr. Bagni used blood from healthy blood

donors whose blood tested negative for known pathogens

typically screened for by blood banks.

To be declared positive, the blood had to show antibodies for

three or more XMRV proteins. The test was able to detect

XMRV but it will likely be refined once more clinical samples

become available, Dr. Bagni said.

She cautioned that the presence of antibodies doesn't

determine if someone has an active infection. Antibodies mean

that someone was exposed to the virus at some point in time.

Kearney, an NCI researcher, took a test she developed

for HIV and adapted it to measure the amounts of XMRV in

patients' blood. The test, called X-SCA, is so sensitive that it

can pick up a single particle of XMRV in a milliliter of blood.

She says the test could be useful in the treatment of patients

infected with XMRV because the test can measure viral loads

before and after therapy.

Carl Hull, president and CEO of Gen-Probe, which has been

working with the XMRV blood-working group, says the company

has an early version test that looks for the genetic material of

XMRV in the blood.

There is a window between when someone is infected and

when the body starts making antibodies that can be picked up

by testing. Gen-Probe says its test enables detection very

early, without waiting for signs of an immune response.

Mr. Hull says the test can be run on an instrument that allows

for high volume testing, which could be useful in screening

blood donors. " We can run 1,000 samples in 14 hours, " he

says.

Kortschak of Roche Molecular Diagnostics says Roche is

still in the earliest stages of developing a research test. He

said Roche wants more " specific proof that XMRV is a virus of

concern and it is possible to transmit through blood

transfusions. "

Another effort attempts to find XMRV specifically in men with

prostate cancer because some research has linked the virus to

that disease. Studies have found the virus in prostate-cancer

tissue, but Klein, a prostate-cancer surgeon at Cleveland

Clinic, says doctors want a way to avoid having to do tissue

biopsies.

Instead, researchers in Dr. Klein's and Dr. Silverman's labs,

developed a test that can detect XMRV genetic material in

urine.

Biopsies sample only a small part of the prostate and can miss

cancer.

A urine test that looks at secretions from the whole prostate

potentially could be more comprehensive. In data presented by

the Cleveland Clinic researchers at an NIH XMRV workshop in

September, 26% of 120 prostate-cancer patients had XMRV in

the urine, compared with 8.5% of healthy controls.

Now that so many researchers have developed early

versions of different tests, the next step is to see how they

work outside a research setting.

Dr. Busch says the federal blood working group is creating a

set of positive and negative clinical samples that all labs can

use, and has sent out blood to various labs to use as they

fine-tune their tests.

The working group is developing a protocol that instructs labs

on how to handle and process the blood, he says.

For instance, discrepancies in the number of days that elapse

between the time the blood is drawn and tested could make a

difference in results, Dr. Busch says.

" When there is a new agent that we don't know a lot about,

it's always a process, " he says.

Write to Amy Dockser Marcus at amy.marcus@...