The Lundbeck Foundation The Brain Prize 2021 · Information Pack 1 The Brain Prize 2021 INFORMATION PACK The scientists behind the science that has led to new treatments for migraine. 2 The Brain Prize 2021 · Information Pack The Lundbeck Foundation The scientists behind the science that has led to new treatments for migraine. The breakthrough in treatment for migraine was 40 years in the making. The pioneering research journey has now led to award of The Brain Prize 2021. The Lundbeck Foundation The Brain Prize 2021 · Information Pack 3 Four decades of careful research have led to new treatments for migraine that are radically improving the lives of sufferers. An international group of four neuroscientists have discovered a key mechanism that causes migraine, a condition that affects more than a billion people and which according to the World Health Organisation is one of the most prevalent and disabling diseases. Their research paved the way to the development of an entirely new class of migraine-specific drugs called CGRP antagonists which help provide long-term prevention of migraine attacks. For this, the four neuroscientists are receiving the world’s most prestigious prize for brain research – The Brain Prize – which is awarded annually by the Lundbeck Foundation. This year The Brain Prize worth DKK 10 million (€1.3 million) is awarded to: Lars Edvinsson (Sweden) · Peter Goadsby (UK/USA) Michael Moskowitz (USA) · Jes Olesen (Denmark) Professor Richard Morris, Chair of The Brain Prize Selection Committee, explains the reasoning behind the award: “Migraine is one of the most common and disabling neurological conditions affecting humans. The work of the four recipients contributed to the clinically effective classification of the various types of this disorder, and then to unravelling the key mechanisms that cause it. This understanding led to the development of a novel therapy and has opened windows into future ones. Their work on migraine is a remarkable example of bedside- to-bench-to-bedside research that has yielded tangible clinical benefit.” 4 The Brain Prize 2021 · Information Pack The Lundbeck Foundation What is migraine? Migraine is much more than a bad head- trigeminal nerve (which is involved in The work of Michael Moskowitz, ache. It is a serious neurological disease controlling movement of, and sensations Lars Edvinsson, Peter Goadsby and Jes with symptoms that include severe in the face) and the meninges and its Olesen has led to the development of throbbing and recurring head pain, associated blood vessels (the meninges new drugs called gepants and CGRP nausea, vomiting, dizziness, extreme is a thin membrane that surrounds the monoclonal antibody treatments. The sensitivity to sound, light, touch, and brain and is the only structure inside the success of these new treatments is smell. Some migraine attacks can last skull that senses pain). Moskowitz pro- remarkable. They are safe and can even for several days and more than 4 million posed that a migraine attack is triggered reduce the likelihood of future people suffer at least 15 migraine attacks when the trigeminal nerve fibres are migraine attacks. Patients have per month. For many, migraine severely activated, leading to release of chemical remarked that the drugs have “given diminishes the quality of life, including signals that dilate (open up) the blood them their life back”. the ability to work, and can lead to vessels of the meninges. This results in depression, anxiety, and sleep distur- local inflammation which ultimately The human brain is staggeringly bances. The economic and societal costs results in severe head pain. But what was complex which means understanding associated with migraine are extremely activating the trigeminal fibres to cause and treating disorders of the brain high - in the tens of billions of dollars a migraine attack in the first place? Prior remains one of science’s greatest chal- - worldwide. to the intense headache, many migraine lenges. We often hear that a major neu- patients experience auras- unusual sen- roscience discovery “could lead” to Treatments for migraine have been sory experiences such as seeing spots of improved treatments for patients. The available for some time, but they can light, flashes, stars, a brief loss of vision, pioneering work of the four Brain Prize have significant side effects and their or tingling sensations in the face or winners has actually done so. efficacy is incomplete. There was there- hands. These auras usually last for less fore an urgent need to develop new than an hour but they often signal the classes of migraine-specific drugs. The imminent arrival of a migraine attack. problem was that doctors were at a loss Moskowitz provided compelling evidence to understand the origin of a migraine that the highly unusual pattern of brain Migraine facts attack. Examinations of migraine activity that results in the auras may also patients between migraine attacks had activate the trigeminal nerve fibres. not revealed anything out of the NUMBERS OF PEOPLE AFFECTED ordinary. However, a major piece of the puzzle • Migraine affects approximately 1 bil- was still missing. What was the nature of lion people worldwide. the chemical signals released by the tri- • Migraine affects 3 times as many geminal nerve fibres which triggered the women as men. attack itself? Working together, Lars • Migraine also affects a considerable Discovering what Edvinsson and Peter Goadsby showed proportion (approx. 7%) of children. that a recently discovered peptide (a • According to the Global Burden of causes migraine small protein-like molecule), calcitonin Disease Study in 2016, migraine is the gene-related peptide (CGRP), was 2nd leading cause of disability and attacks was key to released from the trigeminal nerve accounts for more than all other neu- during a migraine attack and that it was rologic disorders combined. unlocking new ways a potent dilator of blood vessels in the meninges. Based on these findings PREVALENCE AND BURDEN of treating them. Edvinsson proposed that CGRP may be • Migraine is more prevalent than dia- of crucial importance in migraine, but betes, epilepsy and asthma combined. was the release of CGRP from the tri- • Migraine sufferers experience recur- The breakthrough came when four geminal nerve the cause or a conse- rent headaches of moderate-to-severe internationally renowned neuroscientists, quence of a migraine attack? pain lasting 4 to 72 hours. Lars Edvinsson (Sweden), Peter Goadsby • Severe migraine attacks are classified (UK/USA), Michael Moskowitz (USA) This crucial question was answered by the World Health Organization as and Jes Olesen (Denmark) discovered, by Jes Olesen. He showed that when among the most disabling illnesses, over the course of four decades of work, given to migraine patients CGRP could comparable to dementia, quadriple- a cause of a migraine attack. trigger a migraine attack. He then went gia, and psychosis. on to show that drugs which blocked • The financial burden of migraine on The story begins with Michael CGRP could help treat migraine. the UK economy is estimated at £3.42 Moskowitz, an American and a Olesen’s work was not only crucial in billion per year. This figure takes into Professor of Neurology at Harvard showing a causal role for CGRP in trig- consideration the costs of healthcare, Medical School at the Massachusetts gering migraine, but it also demon- lost productivity through absenteeism General Hospital. His worked showed strated that CGRP could be an import- and disability. that a migraine attack involves an inter- ant new target for developing new action between two key players: the treatments for migraine. The Lundbeck Foundation The Brain Prize 2021 · Information Pack 5 • Migraine can run in families, with SYMPTOMS • Anxiety and depression are signifi- 42% of cases thought to be hereditary. • The pain is often throbbing, can be on cantly more common in people with The genetic causes of migraine are not one side of the head, and is aggravated migraine than in healthy individuals. fully understood but it is generally by physical activity. • A significant proportion of migraine thought to be polygenic, meaning that • Other symptoms include, nausea, sufferers experience auras, most com- multiple mutations in different genes vomiting, and sensitivity to light and monly visual and, less often, tingling may cause the disease. sound. sensations and loss of normal speech. About The Brain Prize SCOPE over by His Royal Highness, The Crown world leading neuroscience research The Brain Prize, the world’s largest brain Prince of Denmark. nation, and of raising public awareness research prize, is Danish and awarded of the brain, brain disorders and the by the Lundbeck Foundation. Each year, PURPOSE importance of brain research. the Foundation awards the prize worth Following the award of The Brain Prize, 10 million DKK (approx. €1,3 million) to recipients engage in a series of outreach NOMINATION AND SELECTION OF one or more neuroscientists who have activities, organised by The Brain Prize THE BRAIN PRIZE WINNERS had a ground-breaking impact on brain team at the Lundbeck Foundation. Only candidates who are nominated by research. The Brain Prize recognises These activities not only celebrate the others will be considered for The Brain highly original and influential advances achievements of the recipients but also Prize. The rewarded research must – in any area of brain research, from basic serve to establish and strengthen collab- from an international perspective – be neuroscience to applied clinical oration within the Danish and interna- outstanding. It is the task of The Brain research, and recipients may be of any tional neuroscience community. The Prize selection committee to decide in nationality and work in any country Brain Prize is also used to engage with each individual case, what characterises around the globe. The Brain Prize was and educate the public about the impor- the research as outstanding and there- first awarded in 2011 and has so far hon- tance, challenges, and breakthroughs in fore deserves the prize.