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  Scientist hopes to cure ALS with virus research
Posted January 24, 2002 in ALS Research

There's no more room on the blackboards that cover a wall in Dave Poulsen's office in the University of Montana's Pharmacy building.

And the items that are chalked out in the scientist's bold scrawl are there to stay, such as: eliminate chronic back pain; reverse and prevent Lou Gehrig's disease; quash epilepsy; wipe out deafness.

"I only stopped because I ran out of chalk and chalkboard," said Poulsen, a gene therapy research specialist new to UM.

As lofty as the goals may sound, Poulsen asserts he is not mad, and neither are the other scientists and medical experts who share his goals. "Is there really a good chance we can pull this off? - I think so," said Poulsen who is collaborating on these projects with other Missoula scientists. "A five- to 10-year time frame is pretty optimistic."

Poulsen's arrival in Missoula from a top-notch East Coast gene therapy center has infused UM with new intellectual energy and a unique calling card: a virus.

Why this can happen, and why it can be done in Missoula and in a state that doesn't even have a medical school is the result of many things. There's timing, vision, grant funding and the recruitment of top scientists at UM. There's also Missoula physicians who have a passion for an outdoor lifestyle and teamwork, say those in the thick of it.

"Research is an important part to both of the institutions' mission," said Richard Bridges, a UM pharmacology professor and director of the Montana Neuroscience Institute, a partnership between UM and St. Patrick Hospital.

"The question in the past few years is not so much of why it is happening here - it's why isn't it?" Bridges said. "With advances in electronics and information technology, moving information has become very easy and efficient.

"We have the talent here, and now we have the resources to do nationally recognized work," he said. "We will have groundbreaking research here, but more importantly, the research will help folks locally - for patients who would previously have to go out of state for treatment and expertise."

Together, the Missoula researchers make up an elite team of well-papered and respected professionals who have collaborated their projects along their lines of expertise, and have pulled in the federal grants and the backing of pharmaceutical companies to make things happen.

Poulsen brings to the research bench his expertise in how to insert critical cells with healthy genes where they are mutated or missing. Diana Lurie is a UM researcher with expertise in the human ear and auditory problems. Peter VonDoersten is a Missoula surgeon who specializes in ear, nose and throat anomalies. Bridges is a nationally known scientist respected for his research with brain-related diseases such as epilepsy, Alzheimer's and malignant tumors.

What makes the research projects outlined on Poulsen's chalkboard so forward thinking is that they fall into a whole new scientific classification called "translational research."

"It's a new form that is midway between basic bench science and clinical therapy, which involves patients at hospitals," Bridges said.

"It is a new middle ground which is at the heart of biotechnology and it's also a leading force in spinoff industries in the private sector," he said. "It's here where the potential is greatest for creating new pharmaceutical companies and new jobs, which of course would greatly benefit Montana."

Leading the way is Poulsen's groundbreaking work in using viruses to transport genes to living cells, said David Forbes, dean of UM's Pharmacy and Allied Health Sciences. But even to Forbes, a man steeped in science, the concept is difficult to fathom.

"The science," Forbes said, "is beyond me."

Viruses get into the system quickly and are a good way to carry healthy, functional genes to depleted tissue.

The beast of burden carrying the research into this uncharted territory is a virus called adneo associated virus, which is not linked with any disease and which most people contract by the age of 10, Poulsen said.

This breed of virus, however, has been genetically modified and engineered so that it is little more than capable of traveling throughout the system.

"Really, it's just a mule that we can stuff full of genetic information we want to send to a cell," he said.

Poulsen has further modified the virus, which is now being put through its paces at UM in research launched recently to reverse deafness in humans, and in research being conducted at John Hopkins University to help people who have amyotrophic lateral scleroris, the fatal nerve disorder better known as Lou Gehrig's disease.

"We couldn't even dream about doing this kind of research without Dave's background, or the clinical expertise of Peter," Diana Lurie said recently while she and the other two scientists were working on one of the mice in their trials.

As with deaf humans, the hair cells in the inner ear of these mice, which are critical to hearing, die off and the animal goes deaf.

With Poulsen's virus, Lurie's research background on deafness and VonDoersten's surgery skills, the scientists hope they can regenerate the hair cells in the ear by getting the specific gene responsible for doing the job into the inner ear cells.

The first step, which the scientists are working on now, is to see if they are on the right trail to the inner ear by injecting dye into what is essentially an entryway to the area - through a membrane called the oval window.

Once the path to the cells has been verified with the dye, VonDoersten will inject the mice with Poulsen's virus loaded with the genes that help regenerate hair cells.

"For me this is really a study in comparative anatomy - it's amazing," VonDoersten said. "The similarities between these mice and humans are great, with just a little variation."

The goal is to develop a successful, scientific model with the mice, then move on to monkeys, and then hopefully, move on to clinical trials with humans in the next five to 10 years.

"These things can take years and genetic engineering stuff is still fairly novel," VonDoersten said. "It's not easy to insert genes into viruses, and it's not easy to get to the point where the virus is inserted into the cell.

"But with this virus, it is really promising," he said. "And this is exciting for hearing because nobody has ever done this kind of research on this level, of using live animal models. Usually, we are using information grown from test tubes and petri dishes."

Copyright © 2002 LexisNexis, a division of Reed Elsevier Inc. All rights reserved.

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