Saturday, September 20, 2008

Gene therapy for chronic pain enters first human trial | University of Michigan Health System

ANN ARBOR, Mich. —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 David Fink, M.D., Robert 
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.”

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