A Reboot for the Immune System
Posted on 16. Mar, 2010 by admin in Future, Medicine
The ability to reprogram the immune system is one of the most sought-after goals in medicine. Now researchers are closer than ever to pulling it off in patients with Type 1 diabetes.
A sign rests on the windowsill in the office of Jeffrey Bluestone, director of the Immune Tolerance Network and the Diabetes Center at the University of California at San Francisco. Measuring nearly three feet across, it reads “Club Bluestone” in pink and blue neon. It’s the sort of artifact you’d expect to find in a bar. But Bluestone is a world-renowned immunobiologist; his father-in-law had the sign made for him in the late 1980s when Bluestone was working long hours in his lab at the University of Chicago. As the night wore on and their energy faded, he and his colleagues would turn out the lights, turn on the sign and, propelled by the power of Bruce Springsteen, push forward with their research. “It was our version of partying,” he says.
Bluestone has worked in that lab and ones like it for almost 30 years, wrestling with one of the most vexing problems in medicine: how to keep the immune system from attacking the body itself. It’s been a challenging three decades. Immune researchers work on a biological defense system that’s comparable to the world’s greatest military. This military has millions of potential enemies but no clear leader; instead its members are on constant patrol, a hair trigger away from launching an attack. It’s a recipe for anarchy. Yet the majority of the time, the immune system knows when to hold back. Using processes we still don’t fully understand, a healthy person’s immune system is able to draw a clear line between the body’s own tissues, which it leaves untouched, and invaders, which it identifies and destroys.
The immune system can also be devastatingly destructive. The body’s tendency to reject organ transplants, attacking them as if they were dangerous foreign invaders, is well known. But more prevalent are autoimmune diseases, in which your immune cells attack your own tissues and organs. Left unchecked, these malfunctions can result in one of more than 80 known conditions, including Type 1 diabetes, rheumatoid arthritis, lupus, multiple sclerosis, inflammatory bowel disease and psoriasis. According to the Autoimmune Related Diseases Association, conditions like these affect more than 50 million Americans.
The perfect immune-modulating drug would target only the part of the system causing the problem. As of now, however, most immunosuppressive drugs work by dampening the entire immune system, which leaves the patient susceptible to short-term problems like infections and long-term afflictions as severe as cancer.
Bluestone, who is now 56, has devoted most of his career to improving on this crude, brute-force approach. In the early days of his “club,” he spent many of those long nights tweaking an organ-transplant drug called OKT3, which he and other researchers thought might also be useful for autoimmune diseases like multiple sclerosis and Type 1 diabetes. The problem was, the drug had severe side effects, including cases in which it sent recipients’ immune systems into a kind of overdrive that could be fatal. Eventually, though, working in mice, Bluestone and his colleagues succeeded in changing the drug’s structure to eliminate these side effects. Then he began investigating what else the drug could do.
In 1987 he joined forces with Kevan Herold, an endocrinologist and researcher who was then a colleague of Bluestone’s at the University of Chicago, and the two began exploring the drug’s effects in mice with Type 1 diabetes, an autoimmune disease caused when a class of white blood cells called T cells mistakenly destroys the cells in the pancreas that produce insulin. As their research progressed, they were thrilled to find that the drug halted the progression of Type 1 diabetes in the mice. Second, the new version appeared to act like a guided missile, targeting problematic cells in the immune system without handicapping the rest of it. Bluestone and Herold began to think it might be possible to use it and other, similar drugs as short-term therapies to “reprogram” the immune system, permanently coaxing it back to its original, balanced state. In the world of immunology, this is referred to as immune tolerance. According to Herold, it is the field’s most sought-after goal. And now, thanks to a number of breakthroughs in targeted immune therapy, that goal seems closer than it has ever been. Jordan Pober, the director of the Human and Translational Immunology program at Yale University, is openly enthusiastic about the state of the science: “We’re in the midst of a revolution in our ability to manipulate the immune system.”
By 1995, Bluestone and Herold were eager to move from mouse to man. They wanted to see if the drug could also have a positive effect on Type 1 diabetes in humans. It wouldn’t be a total cure, but if the drug could stop the normal course of the disease—which usually gets progressively worse over the course of a person’s life as the body finishes killing off the cells that produce insulin—it would be a major breakthrough. So in 2000, they launched a trial of the modified drug.
Victorina Beasley
Mar 18th, 2010
This is a great post, im happy I came across this. Ill be back later to check out other posts that you have on your blog.