Gene therapy for chronic pain gets first test in people

[Guest guest]

Gene therapy for chronic pain gets first test in people

http://www.eurekalert.org/pub_releases/2008-09/uomh-gtf091508.php

This week, University of Michigan scientists will begin a phase 1

clinical trial for the treatment of cancer-related pain, using a

novel gene transfer vector injected into the skin to deliver a pain-

relieving gene to the nervous system.

A gene transfer vector is an agent used to carry genes into cells. In

this groundbreaking clinical trial, the investigators will use a

vector created from herpes simplex virus (HSV) – the virus that

causes cold sores – to deliver the gene for enkephalin, one of the

body's own natural pain relievers.

" In pre-clinical studies, we have found that HSV-mediated transfer of

enkephalin can reduce chronic pain, " says Fink, M.D.,

Brear Professor and chair of the department of neurology at the U-M

Medical School. Fink developed the vector with collaborators and will

direct the study.

" After almost two decades of development and more than eight years of

studies in animal models of pain, we have reached the point where we

are ready to find out whether this approach will be effective in

treating patients, " Fink says. The investigators are recruiting 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 that occurs

in many people with diabetes.

The HSV vector, genetically altered so it cannot reproduce, has a

distinct advantage, 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. "

Gene therapy for pain

Chronic pain is an important clinical problem that, despite a wide

array of therapeutic options, cannot be effectively treated in a

substantial number of patients. Fink notes that one key problem in

treating pain is that the targets of conventional pain-relieving

medications tend to be widely distributed in the nervous system, so

that " off target " side effects of the drugs often preclude the use of

those drugs 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. "

Enkephalin is one member of the family of opioid peptides that are

naturally produced in the body. Opioid peptides exert their pain-

relieving effects by acting at the same receptor through which

morphine and related opiate drugs achieve their pain-relieving

effects. In this trial the enkephalin peptide, produced as a result

of the gene transfer, will be released selectively in the spinal cord

at a site involved in transmitting pain from the affected body part

to the brain.

" We hope that this selective targeting will result in pain-relieving

effects that cannot be achieved by systemic administration of opiate

drugs, " Fink says. " This trial is the first step in bringing the

therapy into clinical use. A treatment is at least several years

off. "