Tysabri: The Big Multiple Sclerosis Drug That Emerged From “The Hutch”

The most effective drug on the market today for patients with multiple sclerosis has roots in a dingy old lab in the 1980s on Seattle’s First Hill. It was there that a pair of young scientists at the Fred Hutchinson Cancer Research Center, Bill Carter and Elizabeth Wayner, made key discoveries that paved the way for natalizumab (Tysabri).

The treatment has become the fastest-growing product for Cambridge, MA-based Biogen Idec (NASDAQ: BIIB) and its Irish partner Elan (NYSE: ELN), and it’s projected to generate $1.6 billion in sales in 2011. Most people know of its link to a rare, often fatal brain infection called PML, and its dramatic recovery. But few people know where the drug comes from. So I stopped by Carter’s new lab at the South Lake Union campus of “The Hutch” to hear the story.

Carter, 62, didn’t seem the least bit self-important about this discovery when I stopped by his office last week. He wore a brown T-shirt and brown sandals. Manila file folders with scientific papers were stacked high on the shelves in his office. He didn’t care much to discuss the financial and legal aspects of this story, but when the subject turned to the science, Carter’s eyes lit up with boyish enthusiasm.

He got his doctorate at the University of California-Davis in 1974, where he studied how cells bind to each other, or cell adhesion. After a yearlong fellowship in Israel, he joined the Hutch as a postdoc, shortly after it was founded in 1975. Specifically, he wanted to learn more about the adhesion properties of epithelial cells, those that form linings or boundaries between tissues like skin or other organs. He was interested in these cells because they are involved in most adult cancers.

Those cells remain in a non-active state most of the time, but can become highly activated in the case of an injury, Carter says. For example, when a person falls off a bicycle and scrapes a knee, these epithelial cells leap into action. The cells work to close the wound, secrete proteins that trigger an immune system reaction that mop up all the foreign invaders like bacteria. Other cells, platelets, pour in to the area to form clots.

“Everything is moving in that area to cope with disaster,” Carter says.

This whole process requires big-time changes in cell adhesion properties. By the early to late 1980s, when Carter was pursuing this work on the third floor of Eklind Hall (an old building on Seattle’s First Hill that Xconomy Seattle proudly calls home today), scientists knew very little about this cell adhesion process or the proteins on the surface of cells. “None of the components were known,” Carter says.

One way to identify these components was to develop targeted antibodies that would bind with and block receptors on cells. Carter and his colleagues found GP-140, a new type of protein. This was important because it led to the development of methods to identify more adhesion receptors on the surface of cells, and what they interact with. It was the spark that set Carter and his lab partner Elizabeth Wayner off to the races for the next five years. “We said let’s hunt for different adhesion receptors” on cells, which could serve as new antibody drug targets.

Wayner was one of the scientists who came into Carter’s lab as an immunology postdoc. The biggest step ahead for these two was when they made antibodies that identified a new cell surface receptor called alpha4 beta1. Wayner and Carter, in a paper in 1989 in the Journal of Cell Biology, identified one antibody in particular called P4C2 that they said “completely inhibited” binding to this target. It’s now the target—today called an integrin—which is hit by the natalizumab (Tysabri) antibody.

Carter and Wayner’s work later veered in different directions. … Next Page »

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