Professor Peter McNaughton, King's College London

A new approach to the treatment of migraine

Professor Peter McNaughton was awarded a Brain Research UK project grant in September 2018 for research that aims to take forward our understanding of migraine and how to treat it.

He will further develop work looking at a key part of the signalling process involved in driving the pain in migraine. This will give insights as to how to treat it more effectively.

Following rigorous assessment as part of our competitive project grant round, this project was selected for funding because the members of our Scientific Advisory Panel felt that it would make an important contribution to knowledge in an important area, with high unmet need. The panel liked the straightforward approach, and felt confident that this group could successfully deliver the project.

About migraine

Migraine is a complex condition that is estimated to affect one in seven people. It is more prevalent than diabetes, epilepsy and asthma combined and, because of its prevalence, is one of the leading causes of disability among the neurological disorders.

Migraine has a variety of symptoms, most notably a painful headache. Other symptoms include disturbed vision, sensitivity to light, sound and smells, as well as nausea and vomiting.

The chronic form of migraine affects up to 2% of the population, and is defined as having more than 15 headache days in a month, with at least eight being migrainous. 

There is no cure for migraine, but existing treatments can reduce the severity of attacks in some people, and steps can be taken to reduce the likelihood of attacks occurring.

Read more: Migraine

HCN2 channels: a novel target for treatment of migraine

Pain is initiated when specific pain-sensitive nerve fibres (nociceptors) are activated by painful stimuli - such as heat, sharp force, and chemical stimuli such as acid.

In the last 10 years, progress has been made in understanding the cellular basis of pain – the biological changes that are triggered by contact with these stimuli. In the case of migraine, however, it is not clear how the various stimuli that are associated with the condition actually cause the symptoms. 

Peter McNaughton is Professor of Pharmacology at King’s College London. He leads a programme of research focused on pain, and uses molecular and cellular techniques to find out about the processes underlying pain and sensation. His lab is at the forefront of research into pain.

In this project, Prof McNaughton proposes a new and original idea of how migraine pain may develop and hence, how it may be treated. This is supported by a solid body of preliminary work.

Ion channels are “tiny transportation tunnels” in cell walls that carry out many critically important cell functions, including the regulation of chemical signalling between nerve cells. Malfunction of ion channels can cause a number of different diseases.

Prof McNaughton and colleagues have built a strong case that a family of ion channels called HCN ion channels, in particular the HCN2 ion channel, may essentially be the gate-keepers to migraine. Accordingly they propose that blocking HCN2 could alleviate the symptoms of migraine.

This project will take forward this as-yet-unexplored role for HCN2 ion channels in migraine, to determine whether HCN2 triggers migraine pain, and will stimulate the development of new, more effective therapies for migraine, that act on HCN2 ion channels.

“Professor McNaughton is a word-leading expert in research on nociception and pain mechanisms, and the other applicant (Dr Anna Andreou) is an internationally recognized expert of migraine research. These two collaborators are best suited to work very successfully in combining their experience.” External reviewer.

Impact

Migraine is a distressing and debilitating condition from which many sufferers struggle to achieve effective relief.

It takes a heavy toll on the lives of individual sufferers, impacting relationships and family life, work and wider health. It impacts enormously on society as a whole, through lost productivity.

Current treatments are not effective for all and are associated with a variety of side effects.

This project has the potential to identify a new target for migraine therapy – the HCN2 ion channel. Identifying HCN2 as a fundamental driver of migraine will promote the development of HCN2-selective inhibitor drugs as a novel therapy for migraine. If successfully developed, this could have a major impact on the treatment of patients suffering from this common disorder.

This proposal fills a gap and is an excellent chance for a break-through in the understanding of migraine-generating nociceptive mechanisms.” External reviewer.

Related research projects

Headache is one of our current priority research areas, reflecting the large unmet need in this area. We want to fund research that will help us to understand the underlying causes and mechanisms of headache and facial pain, and help advance diagnosis and treatment. 

Other research projects currently funded under this theme include: