Gene therapy for chronic pain gets first test in people
December 2, 2008
Scientists with VA and the University of
Michigan are launching a phase 1
clinical trial for the treatment of cancerrelated
pain, using a new way of delivering
a pain-relieving gene to the nervous system.
The team will use a gene transfer
vector—a carrier molecule used to ferry
genes into cells—created from herpes
simplex virus (HSV), the virus that causes
cold sores. The vector will carry the gene
for enkephalin, one of the body’s own
natural pain relievers.
"In preclinical studies, we have found that
HSV-mediated transfer of enkephalin can
reduce chronic pain," says David Fink, MD,
a staff neurologist at the Ann Arbor VA and
chair of the department of neurology at
University of Michigan Medical School.
Fink developed the vector with collaborators
over two decades, in part with VA funding.
Fink and colleagues will recruit 12
patients with intractable pain from cancer to
examine whether the vector can be used
safely to deliver its cargo to sensory nerves.
The trial represents two firsts, says Fink:
It is the first human trial of gene therapy for
pain, and the first study to test a
nonreplicating HSV-based vector to deliver
a therapeutic gene to humans. Fink says the
technique may hold promise for treating
other types of chronic pain, including pain
from nerve damage, which often occurs in
The HSV vector, genetically altered so it
cannot reproduce, has a distinct plus, Fink
says: "Because HSV naturally travels to
nerve cells from the skin, the HSV-based
vector can be injected in the skin to target
pain pathways in the nervous system."
Chronic pain is a difficult clinical
problem, explains Fink, partly because the
molecular targets of conventional pain
drugs tend to be widely distributed in the
nervous system. As a result, "off target"
side effects of the drugs often preclude their
use at fully effective doses.
"This provides the rationale for using
gene transfer to treat pain," Fink says. "We
use the vector to deliver and express a
chemical that breaks down very quickly in
the body. The targeted delivery allows us to
selectively interrupt the transmission of
pain-related signals and thus reduce the
perception of pain.
"We hope that this selective targeting
will result in pain-relieving effects that
cannot be achieved by systemic
administration of opiate drugs," says Fink.
"This trial is the first step in bringing the
therapy into clinical use."
This article originally appeared in the Nov/Dec 2008 issue of VA Research Currents.