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The human factor

JMU's Kerry Cresawn ('98) remembers her graduate research in the lab featured in the film "Extraordinary Measures"
By Jan Gillis ('07)

Kerry Cresawn ('98), JMU visiting assistant professor of biology, receives plenty of thank you cards from her students.

Kerry Cresawn ('98), JMU visiting assistant professor of biology, receives plenty of "thank you" cards from her students. "Students are so appreciative that you're on their side," she says.

The recent film "Extraordinary Measures" tells the story of John and Aileen Crowley, desperate parents trying to find a cure for their two small children's rare and fatal genetic disorder.

It's a tale that Kerry Cresawn ('98), JMU visiting assistant professor of biology, relates to, and not just because she was a graduate assistant in the lab that worked on the treatment. For her, scientific research has always had a powerful human component.

"During my senior high school year, my mom died of brain cancer," she says. Before her mother's illness, Cresawn gave little thought to science, including biology; she aspired to be a math teacher. "However when my mom was diagnosed with cancer, I became obsessed with the idea of finding out about the disease and how to fix it," she says. It was the beginning of Cresawn's personal and professional quest for scientific knowledge.

She vividly remembers her undergraduate research experience as a JMU biology major, "It was so positive. Not just the techniques I learned, but the way I learned to think about solving problems, the camaraderie that developed among the student researchers, and the collegial relationships we developed with our professors." The experience yielded another benefit: while doing undergraduate research in the biology lab she fell in love with her future husband. She and Steve ('96), who is also a JMU biology professor today, went to the University of Florida to continue their graduate studies.

Solving the riddle of Pompe disease

There, her mentor, Dr. Byrne, a pediatric cardiologist was researching Pompe disease, a rare, often fatal, disorder that causes sugars in the form of glycogens to build up in the body's muscles. While the body usually breaks these down as needed, the process is impaired in those with Pompe disease. "These children cannot break down the glycogen because the gene that makes the enzyme to do so is mutated. The cells enlarge and problems in the muscle tissues result." Many children die of enlarged hearts or cannot breathe properly. "In the most severe cases, children usually die by the age of two," explains Cresawn.

Byrne, one of the few specialists in the nation treating these young patients, had begun to look into gene therapy as a potential cure.

"The idea is that you give patients the correct form of the gene that is mutated in their cells. The normal copy of the gene will get into their cells and start being expressed, enabling the patient to make the protein necessary to correct the problem."

If successful, gene therapy has the boon of correcting the underlying cause of Pompe disease early on. Unfortunately, getting approval from the U.S. Food and Drug Administration for trials is quite slow and requires meeting demanding criteria at each step of the process.

Different therapies

"One of the obstacles with gene therapy is designing a treatment that is both safe and results in high levels of expression of the new gene. My project was to test different delivery routes and gene therapy vectors to optimize gene expression while also monitoring their immune response," says Cresawn.

Cresawn, who has taught JMU students from freshman to senior level, says she enjoys the challenge of working with students at different levels.

Cresawn, who has taught JMU students from freshman to senior level, says she enjoys the challenge of working with students at different levels.

The lab also tackled a different angle in the fight against Pompe disease — enzyme replacement or protein therapy. And, it was this work that is featured in "Extraordinary Measures."

"In theory, this therapy is much more straightforward. You give patients the proteins that they can't make because their genes are defective," says Cresawn. While not a novel idea, the strategy has not worked for Pompe disease in the past because of the difficulty in making the proteins the way cells in the human body manufacture them. "If the proteins are not exact, they do not get into the body's cells as easily," she explains.

"One researcher, Dr. William Canfield, who was then at the University of Oklahoma, had found a way of making the proteins in such a way that they would get into the cells," says Cresawn, "and the Crowleys got in touch with him because they wanted their children to get the drug." The fictional Dr. Robert Stonehill portrayed by Harrison Ford in the film is based on Canfield and other players in the real-life drama including Cresawn's mentor, Byrne.

"In the movie, Stonehill's response to John Crowley (played by Brendan Fraser) was not too far from reality," says Cresawn. The likelihood of a university professor getting grant funds to work on producing this particular drug for patients was minimal. "The fact is," she says, "manufacturing enough drug to treat just one person is very expensive, and very few people have the disease." Consequently, the drug has a reduced chance of yielding profit.

Crowley, a Harvard trained businessman, and executive with Bristol-Myers Squibb Co., was not deterred. He quit his job and began a successful campaign to raise the venture capital to start a business with Canfield to make the drug in clinical grade quality, so that it could be put through FDA clinical trials.

Research and the human connection

"Before any drug is put in people it must be tested in animals. Our lab was commissioned to take the four potential candidate drugs and inject them into mice with the disease. We then checked the animals' tissues to see if their protein levels and muscle physiology were improved, and we noted any toxicity resulting from the drug."

The lab environment was very different from the typical grad school experience. "Usually you're focused on getting your Ph.D., a few publications and a job," says Cresawn, but she and her fellow lab partners felt a different motivation.

"While the focus of my project was the gene therapy study, all lab members chipped in to assist with the preclinical study for protein therapy. We were all very aware of the importance of the work. We knew the families impacted by the disease," she says.

In fact, the families and researchers grew close. "We went to celebrate one of the children's first birthday at the hospital. The child was very ill. It was the most emotional "Happy Birthday" I ever sang." The poignancy of the moment was particularly vivid; by that time the Cresawns had begun a family of their own. "There was only a month's difference in the age of this very sick little boy and my daughter," she says.

As the work progressed, the biotechnology giant, Genzyme bought out Canfield and Crowley's smaller company. "To run a clinical trial you really do need the manpower, money and name recognition that a big company has. Genzyme manufactured the drug, and children began to get the treatment. That child would not be alive today without it."

Cresawn says she had such a good experience when she did undergraduate research at JMU that she decided she wanted to teach.

Cresawn says, "I had such a good experience when I did undergraduate research at JMU. I decided I wanted to teach."

The medical success story comes at a cost, a month's worth of treatment amounts to thousands of dollars. The fact that protein therapy requires continual injections to sustain a level of health and at such an expense points to the advantage of gene therapy. "If it is successful it is a one-time injection. Then the body's cells take over and begin replicating the DNA," she says.

Cresawn recently learned that the gene therapy research she was a part of has passed initial FDA approval. "Clinical trials are anticipated to start within the year; six infants with Pompe disease will be receiving the drug. That's exciting because there are not a lot of approved gene therapies, especially for rare diseases and especially in children."

While research has its lure, the powerful human factor has influenced her career choice to teach. "Teaching is an incredibly rewarding job. I feel that I can make a difference on a much more personal level than I could doing medical research, and I truly enjoy it," she says looking at her office shelf. There, lined up in multiple rows of colorful cheer, are the cards from her grateful students thanking Cresawn for giving them an exceptional classroom experience.