Research Highlights
New genomics lab in Little Rock will move VA toward ‘personalized medicine’
June 19, 2007
When patients receive the anticlotting
drug warfarin, commercially
known as Coumadin, the dose has to be
just right: Too little won’t prevent clots,
and too much can cause severe bleeding.
Until recently, doctors would have to
carefully monitor patients over several
visits to fine-tune their dose. Now, with a
small sample of a patient’s DNA—usually
from a cheek swab or blood draw—doctors can run a genetic test and predict
the proper dose from the outset.
"Patients still need to be monitored,
but at least we can get close from the
start," says Steven Schichman, MD, PhD,
chief of hematopathology and molecular
diagnostics at the Little Rock VA Medical
Center. The warfarin test is an example of
the work Schichman will be overseeing
as head of VA’s first Pharmacogenomics
Analysis Laboratory (PAL), funded with
$825,000 from VA’s Office of Research
and Development.
The new lab—an outgrowth of a
molecular diagnostics lab Schichman has
run since the 1990s—will also do tests for
veterans who need irinotecan, or Camptosar,
a colon-cancer drug. Certain patients
need more of the drug, but too high a
dose can block breathing and cause other
serious side effects. “We’ll be testing for
a certain enzyme involved in the metabolism
of this drug,” explains Schichman. “If
we can predict which patients are fast or
slow metabolizers, we can adjust the dose
and get it right the first time, so the drug
is at its full therapeutic level but doesn’t
have the toxicity of an overdose.”
Testing on behalf of individual VA patients—for warfarin, irinotecan and eventually
many other drugs—is only part of what
the PAL will do. But this in itself is an important
step toward “personalized medicine,”
says Schichman. “We’re looking at people’s
genetic makeup and using that information
to tailor therapy, to select the drug that’s best
for them, and to select at least a starting dose
that’s most appropriate.”
The PAL will also be a research lab for
VA’s Cooperative Studies Program, which
runs clinical trials involving up to thousands
of patients at multiple sites. Researchers
will collect DNA samples from study volunteers—along with their clinical information—and the PAL will scan the genetic
material to see if certain variations are associated
with particular medical conditions.
Today’s methods allow for fast,
efficient DNA scanning
The scanning is done through a superefficient
method called “high throughput
genotyping.” The process relies on commercially
available chips encoded with
up to half a million or so common genetic
variations. Scientists now have a complete
picture of humans’ genetic structure, thanks
to the much—publicized Human Genome
Project and other gene-mapping efforts.
‘We’re looking at people’s
genetic makeup and using that
information to tailor therapy.’
By scanning huge batches of DNA for the
variations encoded on the chips, researchers
have already linked some of these variations—known as single—nucleotide polymorphisms,
or SNPs for short—to diabetes,
breast cancer and other diseases. The concept
has been around a while, but the mindblowing
speed and relative ease of the new
technology allows for the statistical power
researchers need to show meaningful links
between genetic variations and diseases.
Linking genetic variations to
disease is only part of the puzzle
Schichman acknowledges that linking
a SNP to a particular health condition is
one thing, but understanding how exactly
the risk plays out is quite another. Genetic
variations may determine our health to a
large extent, but only through an amazingly
complex process that involves multiple
genes and any number of environmental
factors.
"Once the associations are pinpointed,
the science needs to be done to show
mechanistically how those associations may
lead to, for example, higher susceptibility to
a certain cancer," says Schichman. His lab
team will work with molecular epidemiologists
at the Little Rock VA and other sites
to plan research and analyze the data that’s
collected.
Even though there’s much work yet to be
done, Schichman compares the completion
of the human genome and the new technology
it has spawned to a burst of light that is
enabling exponential progress. "It’s really
very exciting. I started in this field a long
time ago, and we were in the dark about so
many things. Now, there’s so much more
that we can do."