Advances in Migraine Research
Brain Prize 2021 – Treating migraines
The 2021 Brain Prize was awarded to an international group of four neuroscientists, Lars Edvinsson (Sweden), Peter Goadsby (UK/USA), Michael Moskowitz (USA), Jes Olesen (Denmark), for their pioneering research that uncovered a key mechanism that causes migraine. Their research paved the way to the development of an entirely new class of migraine-specific drugs called CGRP antagonists which help in the long-term prevention of migraine attacks that affect a billion people worldwide.
Much worse than a bad headache, migraines are one of the most common and disabling neurological conditions affecting humans. For many, migraine severely diminishes quality of life, including the ability to work, and can lead to depression, anxiety, and sleep disturbances. Treatments have been available for some time but can cause significant side effects and don’t always work. There was an urgent need to develop new classes of migraine-specific drugs.
For a long time, scientists were at a loss to explain the origin of migraine attacks, handicapped by the lack of satisfactory animal models that only became available in the second half of the 20th century. There was no consensus on whether migraine headaches arose from inside or outside the cranium, or whether migraine was an organic or psychological disorder. There were no animal or tissue models and no pathology. Treatment options were suboptimal and the field lacked any coherent theoretical structure.
Discovering the causes of migraines was key to unlocking new ways to treat them. The work of the four recipients of the 2021 Brain Prize, over the course of four decades, contributed to the clinically effective classification of the various types of migraine, and then to unravelling the key mechanisms that cause it.
The story begins with Michael Moskowitz, who showed that a migraine attack involves an interaction between two key players: the trigeminal nerve (involved in controlling movement of, and sensations in the face) and the meninges (a thin membrane that surrounds the brain and the only structure inside the skull that senses pain) and associated blood vessels. Moskowitz provided compelling evidence that highly unusual patterns of brain activity can activate the trigeminal nerve fibres, leading to the release of chemical signals that dilate the blood vessels of the meninges. This results in local inflammation which ultimately results in severe head pain. Today Moskowitz continues his work in animal models of migraine and in the exploration of migraine genetics.
However, at the time, a major piece of the puzzle was still missing: the nature of the chemical signals released by the trigeminal nerve fibres which triggered the attack itself. Working together, Lars Edvinsson and Peter Goadsby showed that a recently discovered peptide, calcitonin gene-related peptide (CGRP), was released from the trigeminal nerve during a migraine attack and that it was a potent dilator of blood vessels in the meninges both in humans and experimental animal models they had developed. Jes Olesen went on to prove that CGRP could trigger a migraine attack in mice, and that CGRP could be an important new target for developing new treatments for migraine. He found that drugs which blocked CGRP could help treat migraine.
This understanding led to the development of a novel therapy and has opened windows into future ones. The work of Michael Moskowitz, Lars Edvinsson, Peter Goadsby and Jes Olesen both in animals and humans led to the development of new drugs called gepants and CGRP monoclonal antibody treatments. The success of these new treatments is remarkable. They are safe and can even reduce the likelihood of future migraine attacks. The work of the four researchers on migraine is a tremendous example of bedside-to-bench-to-bedside research that has yielded tangible clinical benefit.
More information :
https://lundbeckfonden.com/files/media/document/Information_Pack_TheBrainPrize_22.02.21.pdf
Last edited: 28 February 2025 16:10