ERC Synergy Grant advances understanding of the blood–nerve interface to improve pain management

(Press-News.org)
Tambet Teesalu, University of Tartu Professor of Nanomedicine, has been awarded an ERC Synergy Grant to study the blood-nerve barrier – the interface between blood vessels and nerve cells – in search of solutions to shortcomings in pain treatment. 

Teesalu’s research group, in collaboration with colleagues from the United Kingdom, Italy and France, will focus closely on the peripheral nervous system to create a detailed molecular and spatial map of the blood-nerve barrier and therapeutic approaches that could influence it. Their work will, among other applications, contribute to a better understanding and treatment of nerve pain, which affects nearly one fifth of the world’s population. 

Blood-nerve barrier as a protective shield of the nervous system 

When we speak of the human nervous system, we usually picture the brain and the spinal cord, with a network of nerves branching throughout the body, influencing our sensations, movement, internal organ function, and reflexes. Less well known, however, is the fact that the functioning of this neural network and the impact of diseases on the nervous system are closely linked to the blood vessels connected to nerve tissues. Nerves and blood vessels develop together and remain in contact throughout life, forming a unique protective mechanism at their interface – the blood–nerve barrier, which shields nerve cells from harmful substances. Blood vessels also supply nerves with nutrients and aid in recovery from injury. 

Damage to the blood-nerve barrier is strongly associated with many conditions requiring pain management, such as different inflammatory conditions and nerve damage caused by diabetes or anticancer therapy. However, the molecular-level functioning of the blood–nerve barrier has not yet been thoroughly studied – how blood vessels help repair injured nerve cells, what mechanical forces influence the barrier’s function, and how medicines could be targeted specifically to the cells connected to nerves via this barrier. 

European research supergroup 

With the support of the ERC grant, four leading research groups from across Europe will join forces for the next six years. Professor of Cardiovascular Biology Ellie Tzima from the University of Oxford will investigate how mechanical stress influences the biological processes of the blood-nerve barrier. A team led by Dario Bonanomi at San Raffaele Hospital in Italy will focus on neurobiology and the mechanisms involved in nerve fibre structure and regeneration. Isabelle Brunet’s group at the Collège de France will bridge neuroscience and vascular biology. Tambet Teesalu’s team will explore how to deliver drugs across the blood-nerve barrier using special molecules – homing peptides – that help guide medicines to the right cells. 

“Just as every street has its own zip code, the blood vessels in our body have unique molecular zip codes that allow homing peptides to direct medicines precisely to the right location. So far, we have worked extensively on targeting solid tumours and the brain, but the peripheral nervous system is a relatively new area for us,” explained Teesalu. During the project, the researchers will identify molecules suitable for crossing the blood-nerve barrier and aim to improve their binding properties to enhance future treatments. 

“We expect to reach understanding of how to better tackle chronic nerve pain, for example. Clinical applications of the findings will be still a long way off, but with this project, we are opening up a new field of research that lays a strong foundation for eventually being able to help patients,” said Teesalu.  

Tambet Teesalu is the only Estonian researcher to have received ERC funding three times. He was awarded a ERC Starting Grant in 2012 and a Proof of Concept Grant in 2018.  

The project “Unlocking the neurovascular interface of peripheral nerves in homeostasis, disease and repair” lasts for six years and its total budget is 10 million euros, 2.5 million of which is assigned to Teesalu’s research group. A total of 712 applications were submitted in this round of the ERC Synergy Grant call. 

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