Duke researcher's persistence pays off with new drug for gout

The line of work Dr. Mike Hershfield has pursued for most of his 32-year research career at Duke University is basically scientific social service.

He adopts orphans.

Specifically, he takes on so-called orphan diseases -- afflictions so rare that the big pharmaceutical companies have no financial incentive to develop treatments.

Hershfield and his team at Duke are among more than a dozen research groups at Duke, UNC-Chapel Hill and private biotech companies in the Research Triangle Park area that have contributed to a wave of new treatments for people suffering from diseases such as immune disorders, rare cancers and cystic fibrosis. Each disease afflicts fewer than 200,000 Americans, but all the orphan diseases added together strike an estimated 25 million.

Under the federal Orphan Drug Act, passed 25 years ago, grants and exclusive marketing rights are extended to researchers who develop drugs for rare diseases. But the work of finding treatments is still often patched together with small grants, fragile collaborations with private companies -- and a tiny group of patients desperate for a breakthrough.

For Hershfield, 15 years of work culminated last week in an announcement at a scientific meeting that the drug he helped develop for people with untreatable gout proved effective in a large trial. Perhaps as early as 2009, the treatment may be available to an estimated 40,000 people who suffer from gout and get no relief from the predominant therapy.

"My goal from the very beginning was to provide treatment for people who had absolutely nothing else," Hershfield said. In his clinical work as a rheumatologist, he said, he often tends patients in desperate pain from untreatable gout.

Like many who delve into research on rare diseases, Hershfield got involved through a combination of expertise and coincidence.

A medical doctor who also has an appointment in the biochemistry department at Duke, he had worked on another treatment at Duke in the 1980s. It was for babies born with an exceptionally rare enzyme deficiency that resulted in a failed immune system.

A new approach

A child at Duke had not been cured of the immune disease despite two bone-marrow transplants. Doctors wanted to test a new approach -- replacing the missing enzyme by attaching it to a large molecule called a polymer and infusing it into the child's bloodstream.

After treatment, Hershfield's lab tested the enzyme levels in the child's blood. He found that the polymer, which isn't absorbed by the body, enabled the enzyme to circulate much longer and work more effectively. The child was saved, and the technology of fusing the so-called PEG polymer with biological therapies began to be applied in other long-lasting treatments.

By happenstance, Hershfield learned that the company that had produced the lifesaving drug for the immune disorder had developed another potential therapy with the polymer. It was for gout -- a disease in which uric acid builds up in the joints, causing inflammation and pain. Hershfield knew firsthand how such a therapy would help his patients. He urged the company to fine-tune its approach so that a drug could be tested in people.

After six years, however, the company decided it wasn't interested in pursuing the drug, so in 1993, Hershfield decided to press forward on his own. To qualify for a small grant from the National Institutes of Health, he needed to line up another company.

Finally, a startup company in California, Mountain View Pharmaceuticals, indicated it was interested. By 1996, Hershfield and his research partner at Duke, Susan Kelly, won more federal grant money and began testing the technology on mice that had been specifically bred to have gout.