Gene therapy making comeback after French success

Posted: Friday, May 03, 2002

ALAMEDA, Calif. (AP) -- Companies pursuing gene therapy cures are quietly regaining lost momentum and claiming vindication after experiments in France apparently helped rid four ''bubble boys'' of their immune deficiency diseases.

Alameda-based Avigen is one such business. It recently received federal approval to resume human tests on Coagulin-B, its gene therapy for hemophilia.

Onyx Pharmaceuticals Inc. of nearby Richmond, Calif. is another. Its gene therapy for several different cancers, including pancreatic and colorectal, are in human trials.

The positive publicity is a a welcome change for gene therapy researchers who believe their field was hyped beyond reality in its infancy a decade ago only to be unfairly disparaged after Jesse Gelsinger, 18, died in September 1999 during a gene therapy experiment at the University of Pennsylvania.

Several other clinical trials involving gene therapy also were tainted with accusations of sloppiness and suspended after Gelsinger's death, believed to be caused by a massive immune system reaction to the gene therapy.

But plenty of human testing, such as at Onyx, continued without interruption.

''After all the trauma, things now appear to have turned the corner for us,'' said Dr. W. French Anderson of the University of Southern California, who performed the world's first gene therapy attempt in 1990. ''Some people left the field. But those that stayed are starting to make real progress.''

Gene therapy research aims to cure everything from simple, one-gene defects like hemophilia to complicated diseases like cancer by injecting helpful DNA into patients.

For some patients, gene therapy is their last chance.

''It has dramatically improved my life,'' said Rev. Charles Wilson, 58, of Charlotte, N.C., who suffers from heart disease.

In 1998, his doctors told him that after two bypass operations that there was nothing they could do to relieve the 25 daily angina attacks he suffered. So in 1999, Wilson enrolled in an experimental gene therapy program in Boston where doctors injected the gene for vascular endothelial growth factor into areas of dead heart muscle.

Today, Wilson said he occasionally suffers two mild angina attacks in a day. ''I couldn't walk more than 100 yards before gene therapy,'' he said. ''Now I'm back to normal.''

The hope is that one or two injections every few years of helpful genes -- delivered using harmless versions of viruses known as ''vectors'' because they are adept at entering cells -- can replace the daily and weekly injections some diseases now require.

The four bubble boys, who suffered from the deadly severe combined immunodeficiency, were given gene therapy in 1999 and 2000 when they were babies.

All four, followed for up to 2 1/2 years, are thriving.

''This is most promising for gene therapy,'' said Matt Geller, an analyst with CIBC World Markets Corp.

Investors and researchers who abandoned the field soon after Gelsinger's death are now slowly returning.

After Gelsinger's death, applications to the Food and Drug Administration to conduct gene therapy trials on humans dropped.

In fiscal year 1999, the agency received 55 new applications to start clinical trials, the most ever received in a single year.

In 2000, the applications fell to 31 but picked up last year to 36. In 2002 so far, the agency has received 14.

More applications are expected as promising results are reported from ongoing clinical trials.

Some 2,200 patients are enrolled in about 470 gene therapy trials in the U.S.

And though the FDA has yet to approve a gene therapy drug for sale, at least four products are in Phase III human trials, the last stage before seeking such approval.

''People are coming around to the realization that there are tremendous benefits to gene therapy,'' said Avigen chief executive John Monahan.

He has good reason to be optimistic.

In December, Avigen received FDA approval to resume human testing of its hemophilia treatment.

Avigen uses a harmless virus found in 90 percent of the world's population to deliver a blood-clotting gene that is missing or broken in hemophiliacs.

The company temporarily suspended the human trials in October after it discovered trace amounts of the genetically engineered virus in a patient's semen. After testing showed the virus in the semen wouldn't pass to the patient's offspring, the FDA allowed the Phase I trial to resume.

Still, Avigen's testing delay highlighted one of the field's biggest ethical concerns: preventing altered genetic material passing from patients to their children.

Some fear altered genes could be passed on to future generations, which they view as re-engineering the human species that could lead to unexpected side effects in future offspring.

There are other big challenges for researchers:

Delivering enough of the helpful genes to their targets in the body, controlling how they act -- and keeping them active long enough to be effective.

There is also a fear that a genetically engineered virus will interrupt the function of targeted cells and cause cancer.


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