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From Bench to Bedside:
Blocking Pain From the Brain
Researchers study use of gene therapy to treat chronic cancer pain

Blocking Pain from the BrainU-M researcher David Fink, M.D., has worked for 20 years to develop a gene-transfer vehicle that releases pain medication in the affected nerve pathways to block pain transmission from the spinal cord to the brain.

University of Michigan researchers have launched the first study to determine whether it’s safe to use gene therapy to treat chronic cancer pain. The study—a prime example of translational research—marks a pivotal moment. Researchers now have an opportunity to learn whether what they’ve discovered in the laboratory applies in humans.

The Concept: Targeting the Pain

Doctors have several ways to treat chronic pain, but many medications produce side effects strong enough to prevent people from using these drugs at fully effective doses. U-M researchers are working on ways to use gene therapy to deliver pain relievers to precisely targeted sites within the body.

Blocking Pain from the Brain“Because the body uses the same receptors and neurotransmitters in many different places in the nervous system, medications we use often result in off-target effects that limit the dose we can administer,” says David Fink, M.D., Robert Brear Professor and chair of neurology at the U-M Medical School. “Our goal was to develop a gene-transfer vehicle—a vector—that releases substances precisely in the pathways affected to block pain transmission from the spinal cord to the brain.”

Fink and his co-workers created a crippled form of the herpes simplex virus that they tested extensively in animal models. HSV is ideal for delivering genes to sensory nerves because of the natural biology of the parental virus. For the study, the HSV vector is modified to carry the gene for enkephalin, an opioid peptide naturally produced in the body. Opioid peptides act on the same receptors through which morphine and other drugs achieve pain relief.

Steps Toward a Human Trial

Gene therapy for pain was effective in earlier animal studies using rodents and has reduced pain-related behaviors in rodents with cancer pain.

Blocking Pain from the BrainDavid Fink, M.D., meets with colleagues Frank Worden, M.D., and Susan Urba, M.D.With the support of National Institutes of Health funding, Fink has studied herpes simplex virus vectors for 20 years and gene therapy for pain for 10 years. The Phase 1 trial, funded by the Swedish biotechnology company Diamyd Medical, is the culmination of many years of research conducted by Fink and his wife, Marina Mata, M.D., also a U-M professor of neurology.

“This is a clear example of translational research,” Fink says. “We began making the virus in the laboratory, we spent many years testing it in animals and now we are bringing it to people who may benefit.”

Twelve patients with cancer pain are participating in the Phase 1 clinical trial, the first step in the FDA’s drug approval process.

Treatment Tomorrow: Conquering Pain with Vectors

Bringing gene therapy to the marketplace will take time. The Phase 1 trial will be finished by next year, when Fink hopes to begin Phase 2 with a larger group of patients.

“I’ve relied tremendously on institutional resources to move from the lab to the human trial,” Fink says. “The Michigan Institute for Clinical and Health Research and Cancer Center Clinical Trials Office have provided invaluable advice and support. It’s one thing to conduct experiments in a lab and another thing entirely to enroll patients in a study.”

This March Fink will present a proposal to test a similar HSV vector carrying a different gene to treat pain from nerve damage in patients with diabetes. The presentation is at the public review meeting of the NIH Recombinant DNA Advisory Committee in Bethesda, Md. —JD

Comment on this article

"My 84 year old mother developed shingles six years ago and has continued to suffer the extreme pain of the neuralgia. She has tried many different medications but nothing relieves her pain. Although it might be too late to help her, I'm so glad to hear that this is being studied." - Kathy Smith, Internal Medicine - Human Resources


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