Gilla Kaplan

January 11, 2008
by findingDulcinea Staff
Our weekly feature, "Celebrity Through the Ages," tells how prominent people have vied for public attention for centuries. Yet today we feature a world-renowned scientist whose name you likely have never heard, even though the fruits of her research are constantly in the science, health, and business headlines, particularly this week.

International Path to Discovery

According to a 2006 profile in the University of Medicine and Dentistry of New Jersey’s magazine, Dr. Kaplan was raised and educated in Israel and did her graduate work in Norway, at a university above the Arctic Circle. She devoted considerable time to research of prevalent medical conditions caused by mycobacterial infections in Brazil, India, Nepal, Bangladesh, Thailand, the Philippines, and most recently, South Africa, where she is developing a vaccine for newborns at the behest of the Bill and Melinda Gates Foundation. “I have focused on immune-system modulation,” she told the magazine. “We’ve been probing, perturbing, stimulating, and suppressing the immune system as a way of resetting it, to understand its complexity and how it contributes to disease.”

Our Beyond the Headlines section today reviews encouraging preliminary results in reversing the effects of Alzheimer’s disease. The drug used, Enbrel, inhibits the effects of Tumor Necrosis Factor Alpha (TNFa), which is a cytokine, or hormone, that governs the immune response in a human body. Modulating TNFa is at the core of a substantial number of groundbreaking treatments currently being used or studied around the world; the tremendous commercial potential for many of these drugs was presented at the JP Morgan Annual Healthcare Conference this week in San Francisco. But any discussion of modulating TNFa necessarily includes the remarkable research career of Dr. Kaplan.

Following Where Curiosity Leads

Dr. Kaplan spent 19 years as an immunologist at The Rockefeller University in New York. Kaplan devoted her efforts to studying the underlying causes of tuberculosis and leprosy.

In 1991, Kaplan learned that thalidomide, which had caused birth defects in tens of thousands of babies four decades earlier, had also been used to treat leprosy patients in Israel. Curious about thalidomide’s mechanism of action, Kaplan learned that patients with leprosy and its variants had elevated levels of TNFa. Kaplan soon established that thalidomide works by decreasing circulating levels of TNFa.

Kaplan knew that excess levels of TNFa were found in a family of diseases known as “auto-immune” that include rheumatoid arthritis and Crohn’s disease. Of most immediate relevance was the fact that many of these conditions were being seen in the newly exploding population of AIDS patients in the U.S.

A Valuable Chance Encounter

Kaplan was excited about the commercial potential for thalidomide, and she applied for and received a patent covering the use of thalidomide to modulate TNFa. But she had no success convincing any company to commercialize such a notorious drug. Fortuitously, David Stirling, head of research for Celgene Corporation, a small biotechnology company based in New Jersey, consulted Kaplan about a potential treatment for tuberculosis in AIDS patients. After the discussion, Kaplan told Stirling that thalidomide was the drug he should investigate. Stirling was shocked; he wondered if he could create a derivative of thalidomide that offered its benefits without the side effects.

But thalidomide’s potential to treat debilitating conditions associated with AIDS quickly became known, and “buyer’s clubs” formed to illegally import and distribute thalidomide to the AIDS community. The Food and Drug Administration, which had famously refused to approve the sale of thalidomide in the United States in the 1950s, encouraged Celgene to submit a new drug application for approval, and thalidomide was approved for sale in the United States in 1998. At about that time, its potential in cancer treatment also become known, and Celgene acquired the rights to commercialize this body of research. Thalidomide has proven to be an astounding commercial success.

Around the same time, the work that David Stirling and his team had begun after their meeting with Gilla Kaplan produced a viable product, now known as Revlimid. Initial studies suggested that it could be far more powerful than thalidomide, without the same side effects. Revlimid has now been approved in the U.S. to treat multiple myeloma and myelodysplastic syndromes (MDS), and has shown promise in many other diseases. It is expected to generate more than $1 billion in sales in 2008. Celgene, which had a market value of $100 million when it came across thalidomide, now has a market value of $20 billion, due in no small part to its chance encounter with Gilla Kaplan in 1991. Celgene is also working on several other very promising derivatives of thalidomide.

Current Research, Future Rewards

For the past 11 years, Kaplan has spent a significant portion of her time in South Africa, studying tuberculosis and training researchers there, as well as working on a newborn vaccination project backed by the Gates Foundation in South Africa.

Kaplan is now a Professor and full member of The Public Health Research Institute Center at The University of Medicine and Dentistry of New Jersey. Her focus continues to be on harnessing elements of the immune system. She predicts that “[m]aybe what will be most striking in the future about our ability to cope with disease, and protect the body itself, is how capable we are going to become at directing our immune systems. We won’t just be chopping out cancer … [w]e’ll be harnessing the body’s immune response to fight it.”

The Center’s Web site catalogs her recent articles and current research focus.

Kaplan has also served as a member of the Board of Directors of Celgene since 1998.

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