Monoclonal antibodies and small-molecule antagonists that target CGRP or its receptor are already having a big impact on migraine. But they have the potential to do so much more.

Peter Goadsby sat in the audience, intrigued. The Australian medical student had come to Lund, Sweden, for a conference in June 1985. He was studying migraine, and during this particular talk about the trigeminovascular system — the network of nerves linked to blood vessels in the head — something clicked. This pathway, he realized, could be a way to understand migraine.

He introduced himself to the speaker, a physician at the local university hospital named Lars Edvinsson. Over coffee, the two discussed potential biomarkers for migraine in the trigeminovascular system — including a molecule called calcitonin gene-related peptide (CGRP) that had been discovered a few years previously. CGRP is a neuropeptide, which neurons use to communicate, and Edvinsson suspected it had a key role in migraine. The conversation launched a partnership that laid the clinical foundation for a class of drug that, 35 years later, is bringing relief to people with migraine.

“It started as a pursuit of a marker, of asking the question of what might be involved in the pain,” says Goadsby, now a neurologist at King’s College London. “It ended up being bigger than that.”

Since 2018, the US Food and Drug Administration (FDA) has approved six drugs that block either CGRP or its receptor. The drugs are similarly effective to current therapies, but they have had a dramatic impact, thanks to their relative lack of side effects and the fact that they work for many people for whom other drugs fail. “They don’t work for everybody by any means,” says Andrew Charles, a neurologist at the University of California, Los Angeles. “But the potential for that kind of life-changing response is really something I’ve never experienced before.”

Researchers are now looking to treat other kinds of headache with the same CGRP-targeted drugs. But despite the success of these drugs, the role of CGRP in migraine is not fully understood. By probing how the molecule contributes to the hypersensitivity to sensory inputs that is characteristic of migraine, researchers are teasing apart the complex underpinnings of the disease — which could lead to yet more therapies for migraine.

 

Read more here.

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