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2004
WELCOME
FROM VICE PRESIDENT DAN DWYER
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A ROUNDUP OF UM SCIENCE NEWS
PHARMACY
SCHOOL
ON THE GROW
SCHOOL
OF THE MIND
BRAIN STUDIES MAY COMBAT CENTRAL NERVOUS SYSTEM DISEASES
PATHWAYS
OF LIFE
NEW LAB TACKLES VASCULAR DISEASE
GENETIC
HEALING
BIOLOGIST SEEKS DNA-LEVEL CURES FOR HEARING LOSS, CANCER PAIN
HIGH
TECH INSTRUMENT CENTER
SUPER COMPUTING AIDS UM RESEARCH
RETURN
TO BLACK MOUNTAIN
LESS THAN A YEAR AFTER FIRE, NATURE THRIVES
EXTREME
LIVING
HOT POOL CREATURES MAY OFFER GLIMPSE OF LIFE BEYOND EARTH
TUNNELS
TO SAFETY
ANIMALS USE CULVERTS TO CROSS HIGHWAYS
VIENNA
EXPERIENCE
STUDY-ABROAD PROGRAM LEAVES A LASTING IMPRESSION
PROTEINS
MAY UNLOCK MAD COW DISEASE
UM RESEARCHER MICHELE MCGUIRL WORKS TO PROTECT FOOD SUPPLIES
WHEN
SPEECH WASN'T FREE
PROFESSORS DELVE INTO MONTANA'S TROUBLED PAST
FAMILY
ALCHEMY
RESEARCHERS BALANCE SCIENCE, MARRIAGE AND KIDS
CULTURE
CLASH
DIFFERENCES IMPACT ACADEMIC SUCCESS
INVISIBLE
SPACE RAIN
RESEARCHER STUDIES MYSTERIOUS COSMIC RAYS
BRAIN
PAIN
RESEARCHER OFFERS TIPS FOR MIGRAINE SUFFERERS
CAMAS
MAGAZINE
VOICES RISING IN THE WEST
GENETIC
HEALING
Biologist
seeks DNA-level cures for hearing loss, cancer pain
By CARY SHIMEK
Photography by TODD GOODRICH and STEVE KRUTEK
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When Dave Poulsen was a student at Brigham Young University, the concept of gene therapy — sticking a gene into someone to cure a disease — was science fiction, the Holy Grail of molecular biology.
Now a mere 20 years later, Poulsen, a UM research assistant professor, gets to play with that particular Holy Grail every day at work. And the results of his quest could improve the lives of people suffering from hearing loss, cancer pain, even epileptic seizures.
Poulsen, a molecular biologist, has directed the Montana Neuroscience Institute since 1997. A collaboration between UM and Missoula's St. Patrick Hospital, the institute is designed to bridge the gap between pure research and clinical medicine to help those afflicted with diseases of the nervous system.
"I think most people who do this type of work are adrenaline junkies," he says. "It's a fix to be able to solve problems. Plus, I feel that what I'm doing has meaning in the real world and has the potential to improve the quality of people's lives."
So how do you introduce a gene that cures disease? Poulsen says his lab generally uses a benign bug called Adeno-Associated Virus as a mule to transport genetic code to a particular part of the body. The virus is injected and then spreads the required genetic code to areas that need fixing.
He says regular adeno virus causes colds, but Adeno-Associated Virus is defective and doesn't cause any symptoms. And 80 percent of the world's population has AAV floating around inside them by the time they are 10 years old, so the virus makes a good nonpathogenic tool for gene therapy.
Using complex laboratory techniques, Poulsen's crew guts out 96 percent of the genetic material in AAV. Then researchers create circular strands of DNA called plasmids that can be custom-designed with the necessary genetic material to combat a particular disease or condition. This material is then stuffed inside AAV before the virus is introduced to an area of cells afflicted by some malady.
Poulsen says, "Think of a virus as being a tennis ball. The fuzzy yellow is a protein coat, and the inside is full of DNA. So we use the viruses like a mule for transportation. And a mule is a perfect example because these things are sterile. The viruses go into a cell, but they don't replicate."
Once the "mule" trots into a cell, the genetic code it carries hopefully will reprogram the cell to do something new. As an example, Poulsen's group is trying to grow hair cells in the inner ear, which could help improve hearing.
Hair cells are located in a snail-shaped ear organ called the cochlea. When sound waves hit these cells, they move, translating that motion to neurons that feed the brain. That's how we hear. But the cells are fragile, and people on average lose 1 percent of their hair cells per year as they age. For some reason birds and reptiles can regrow hair cells, but mammals cannot.
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| Dave Poulsen at work |
Poulsen's goal is to deliver a gene to cells right next to hair cells in the inner ear and coax them to transform into healthy hair cells. These cells must be arranged in a proper, highly-defined structure for hearing to work. In extremely preliminary tests, his lab has reprogrammed cells to become hair cells in tissue culture, and Poulsen hopes to test the procedure on animals in coming years.
If the animal model works, the procedure would move to clinical trials on humans. Poulsen says he is working on a gene therapy procedure for the ear with St. Patrick Hospital surgeon Peter VonDoersten, who performs cochlear implants.
"But in our procedure, instead of inserting a prosthetic device, we would just inject a virus (into the inner ear)," Poulsen says.
A major stumbling block remains, however. Right now when the scientists grow hair cells in the lab, they appear in random order. Poulsen says they need to figure out a way to get the cells aligned in the proper sequence and attached to neurons in order for hearing to be restored.
"But the potential is there," he says.
Another project the neuroscience institute has tackled involves treatment for bone cancer pain. Currently when someone has bone cancer, surgeons often implant a morphine pump into the brain or spine of a patient to block the extreme pain. Many patients don't respond well to morphine and its side effects.
Poulsen envisions a procedure where gene therapy is used to encode a localized part of the body — such as the spine or a femur — to over-express opiate peptides, which are the body's natural pain killers. (Morphine was designed to mimic them.)
The institute already does gene therapy injections into the spinal cords of rats, causing an over-expression of opiate peptides, and the institute can create bone cancer tumors in rats.
But how do you tell whether you’re alleviating a rat's pain?
"We actually put them in this small Plexiglas chute, where they have both hind feet on separate little scales," Poulsen says. "A normal rat will distribute the weight on its feet evenly. So what we measure is the difference in weight distribution between the right and left. If you have a bone tumor developing, and they never shift their weight, then you know you are blocking the pain. I think this is a good way of testing pain without actually poking the rat. It's the most humane model I've been able to find."
If all this isn't enough, the neuroscience institute and its campus partners also study excitotoxicity — the overstimulation and death of neurons caused by maladies such as stroke and brain and spinal cord trauma. Excitotoxicity also causes epileptic seizures.
Poulsen says neurons communicate with each other using compounds such as glutamate, which gives a stimulating signal, and gamma-amino butyric acid (GABA), which provides an inhibiting signal. After a stroke or before an epileptic seizure, too much glutamate has been released, which could lead to excitotoxicity.
UM researchers are trying to gain a basic understanding of how neurons communicate via chemicals. This could lead to a gene therapy that drives GABA production in the brain, which could reduce glutamate and help prevent seizures — especially for epileptics who don't respond to regular medications.
Though gene therapy is still experimental, its medical applications appear almost limitless. Meanwhile, Poulsen says he enjoys the challenge of trying to turn what he once considered science fiction into science fact.