There's more to treating disease than just finding a target and hitting it, said Oklahoma Medical Research Foundation scientist Joan Merrill, M.D.
In a paper published in the most recent issue of the journal Clinical Immunology, Merrill said new molecular targets in the fight against lupus are exciting. The new treatments are incredibly sophisticated, aimed at bringing tiny proteins in the immune system into balance. But how these treatments work in individual patients is not so simple.
Patients with lupus share certain features in the way their immune systems are disrupted, but they differ in the details of how this comes about, she said.
Lupus is a chronic autoimmune disease caused when the wrong environmental factor encounters a person with a high-risk genetic profile. This causes the immune system to become relentlessly overactive, and the normal checks and balances break down. Eventually there is a great deal of collateral damage, almost as if the immune system has begun mistaking the body's own cells for bacteria or viruses and is attacking them.
Symptoms include fatigue, fever, rashes and joint pain. Lupus affects about 1.5 million Americans, mostly women, and has no known cure. However, more than 30 treatments have entered development recently. Their goal is to finely target various nuanced protein interactions that regulate the immune system.
“The most frustrating thing in trying to get these treatments to work, but also the most fascinating thing when you think about how the body defends itself from invaders, is that the immune system goes around in circles,” said Merrill, who heads OMRF's Clinical Pharmacology Research Program. “We have to be careful, because making one tiny change with some of these futuristic drugs might swing back around and cause a bigger problem elsewhere.”
Merrill said it's best to think of tiny protein disease “targets” as dominos — biological molecules that connect to one or more components of the immune system. Depending on the patient's genetic code, those dominos are balanced in unique ways and may react to medications with an unexpected boomerang effect.
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