Brain Storm Calming
Michael A. Moskowitz was honored for his life's work helping migraine sufferers.
In 1975, Michael A. Moskowitz, M68, a young researcher at MIT, released a report on ten neurological illnesses with unclear etiology. Then he filed them all but one: migraine.
"Around a billion individuals worldwide suffer from migraine," he says. "It's the most frequent neurological illness and the leading cause of disability in people under 50."
Researchers at the time had no understanding what caused the debilitating illness, which causes severe migraines, vomiting, and hypersensitivity to light and sound.
Some hypothesized it was caused by brain blood vessel dilation, platelets in the blood, or sex hormones, as migraine affects women three times more than males. In his opinion it was mostly psychosomatic. Moskowitz put the folder in his right-hand bottom drawer.
"Every time I opened the drawer, I thought about this," he says. After two years of research and study of the brain's anatomy, Moskowitz developed a novel theory: that tiny neuropeptides—small chains of amino acids—that nerve fibers discharge into the brain's covering tissue, the meninges, produce inflammation and other detrimental effects, cause migraine headaches.
Moskowitz was awarded the Lundbeck Foundation's Brain Prize last year. The crown prince of Denmark awarded the medal to Moskowitz and three other researchers who helped discover novel neuropeptide-targeting medications that ultimately bring relief to migraine sufferers.
"I am personally and intellectually pleased that this strategy of finding and targeting these compounds worked," he says. "I went into medicine to help others, and this beyond my expectations."
Growing up in Rockaway, New York, Moskowitz knew he wanted to be a doctor. His father was a doctor who brought him on house calls; Moskowitz was fascinated by the cases. "I made an easy choice," he says. It simplified my life.
Anatomy attracted him at Tufts University School of Medicine, where he won a medal his first year. "The anatomical way to thinking about problems in the nervous system really arose during my first few years as a medical student at Tufts," he explains.
It entailed focusing on the trigeminal nerve, the biggest nerve with fibers on the meninges and associated with migraine-like symptoms. On animals, Moskowitz utilized tracing chemicals to show previously unaccepted transmission of nerve transmitters into the pain-sensitive meninges.
In a few years, he discovered substance P, an 11-amino-acid peptide that causes blood vessels to bleed and increases inflammation. He proved he could reduce the effects of triptans and ergots, two kinds of migraine medicines, by blocking the peptide's release.
A peptide named CGRP was later discovered in trigeminal fibers by British researchers Peter Goadsby and Lars Edvinsson. Dane Jes Olesen developed a medication that targets CGRP without the negative effects of existing treatments, and could be used as a monoclonal antibody to help many patients who suffer from migraines. They all got Lundbeck with Moskowitz.
Moskowitz, a medical investigator at Massachusetts General Hospital since 1990, has focused on an electrical storm of nerve activity that stimulates the trigeminal nerve and releases neuropeptides.
Most people who have migraines have a "aura" of flashing lights and disorientation before they get migraine symptoms. According to Moskowitz, the cortical spreading depression wave might stimulate peptide release from pain fibers, something some experts doubted was feasible in humans.
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