Cystic Fibrosis Trial Shows Promise

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Cystic fibrosis trial shows promise

04/30/03

Harlan Spector

Plain Dealer Reporter

The first human experiments using a gene therapy technique pioneered in

Cleveland appear to have succeeded in correcting the faulty cellular process

responsible for cystic fibrosis.

Researchers at University Hospitals and Case Western Reserve University

began the clinical trial one year ago with 12 patients who received a

corrected gene in a saline solution dripped into their nasal passages.

Cystic fibrosis patients have a genetic defect that causes the buildup of

thick mucus in the lungs and digestive system.

Scientists using a gene-transfer system developed by Cleveland-based

Copernicus Therapeutics Inc. found that the patients suffered no ill effects

and that the therapy appeared to normalize the nasal cells.

The experiment did not attempt to cure the 12 volunteers because the nasal

passages were merely a test site.

Doctors don't know yet whether the gene transfer will take hold in the lungs

or how frequently therapy would be necessary as mature cells die off and

new, defective cells take their place.

But in eight of the 12 patients, the cells produced enough protein to

improve the transport of salt and water, a critical balance that is upset in

cystic fibrosis patients. The gene controls production of the protein

responsible for maintaining the balance.

Doctors are far from fixing the genetic cause of cystic fibrosis, which

affects 30,000 Americans.

" Data is encouraging. We're continuing clinical development, but it's not a

cure yet, " said Dr. Moen, president and CEO of Copernicus.

The eight-employee biotechnology firm has a $1 million state grant to

develop an aerosol technology that will enable the gene to be pumped into

the lungs. Human trials are to begin next year.

The company licensed technology that compacts DNA - the structure that

carries the genetic code - so the corrected gene would be small enough to

enter the cell nucleus. The compacting technology is critical because

viruses that are commonly used to introduce corrected genes into cells are

fraught with problems for cystic fibrosis patients. Early gene therapy

trials caused a devastating inflammatory response.

The 12 patients will have first crack at enrolling in the clinical trial

using aerosol technology for the lungs, said Dr. Konstan, director

of the Cystic Fibrosis Center at UH's Rainbow Babies & Children's Hospital.

" We've got to get it into the lungs, " said Beall, president and CEO

of the Cystic Fibrosis Foundation. " Then I'll call it a breakthrough, if we

see improvement in lung function. "

Stoutenberg, a Cleveland native who lives in Boulder, Colo., has been

closely following the clinical trial. Her 20-month-old son, Jack, has cystic

fibrosis, and she contacted Moen at Copernicus.

" It seems so promising, " she said. " If therapy works . . . Jack can have a

healthy adulthood. "

© 2003 The Plain Dealer.