New Trigeminal Nerve Drugs May Finally Prevent Migraine Headaches
Adam Rifkin stashed this in Medicine
Neurologists believe they have identified a hypersensitive nerve system that triggers migraine pain and are in the final stages of testing medicines that soothe its overly active cells.
These are the first ever drugs specifically designed to prevent the crippling headaches before they start, and they could be approved by the U.S. Food and Drug Administration next year. If they deliver on the promise they have shown in studies conducted so far, which have involved around 1,300 patients, millions of headaches may never happen.
“It completely changes the paradigm of how we treat migraine,” says David Dodick, a neurologist at the Mayo Clinic's campus in Arizona and president of the International Headache Society. Whereas there are migraine-specific drugs that do a good job stopping attacks after they start, the holy grail for both patients and doctors has been prevention.
Migraine attacks, which affect almost 730 million people worldwide, typically last from four to 72 hours. Most sufferers have sporadic migraines and are laid low during 14 or fewer days a month. Those with a chronic form—almost 8 percent of the migraine population—suffer 15 or more monthly “headache days.” Attacks are often preceded by fatigue, mood changes, nausea and other symptoms. About 30 percent of migraine patients experience visual disturbances, called auras, before headaches hit. The total economic burden of migraine in the U.S., including direct medical costs and indirect costs such as lost workdays, is estimated at $17 billion annually.
The breakthrough is in figuring out how to prevent migraines from occurring at all.
The first migraine specific drugs, the triptans, were introduced in the 1990s. Richard Lipton, director of the Montefiore Headache Center in New York City, says triptans were developed in response to the older idea that the dilation of blood vessels is the primary cause of migraine; triptans were supposed to inhibit it. Ironically, subsequent drug studies show that they actually disrupt the transmission of pain signals in the brain and that constricting blood vessels is not essential. “But they work anyway,” Lipton says. A survey of 133 detailed triptan studies found that they relieved headache within two hours in 42 to 76 percent of patients. People take them to stop attacks after they start, and they have become a reliable frontline treatment for millions.
What triptans cannot do—and what Peter Goadsby, director of the Headache Center at the University of California, San Francisco, has dreamed about doing for more than 30 years—is prevent migraine attacks from happening in the first place. In the 1980s, in pursuit of this goal, Goadsby focused on the trigeminal nerve system, long known to be the brain's primary pain pathway. It was there, he suspected, that migraine did its dirty work. Studies in animals indicated that in branches of the nerve that exit from the back of the brain and wrap around various parts of the face and head, overactive cells would respond to typically benign lights, sounds and smells by releasing chemicals that transmit pain signals and cause migraine. The heightened sensitivity of these cells may be inherited; 80 percent of migraine sufferers have a family history of the disorder.
Goadsby co-authored his first paper on the subject in 1988, and other researchers, including Dodick, joined the effort. Their goal was to find a way to block the pain signals. One of the chemicals found in high levels in the blood of people experiencing migraine is calcitonin gene-related peptide (CGRP), a neurotransmitter that is released from one nerve cell and activates the next one in a nerve tract during an attack. Zeroing in on CGRP and interfering with it was hard. It was difficult to find a molecule that worked on that neurotransmitter and left other essential chemicals alone.
As biotech engineers' ability to control and design proteins improved, several pharmaceutical companies developed migraine-fighting monoclonal antibodies. These designer proteins bind tightly to CGRP molecules or their receptors on trigeminal nerve cells, preventing cell activation. The new drugs are “like precision-guided missiles,” Dodick says. “They go straight to their targets.”
The trials look great and I'm hopeful it will be around in the next 5 years. I've heard a lot of talks on this stuff over the past few years and I'm sure it's been discussed a lot in Scottsdale this week. I can't wait. I think insurance companies will pay because an injection every three months or so is probably going to be cheaper than all the pills and crap we take right now.