Colourbox

Researchers to find new paths into the brain

Friday 11 Apr 14

Contact

Thomas Lars Andresen
Head of department, professor
DTU Health Tech
+45 25 37 44 86

The Lundbeck Foundation Initiative on Brain Barriers and Drug Delivery

The Lundbeck Foundation Initiative on Brain Barriers and Drug Delivery is headed by Professor Martin Lauritzen from the University of Copenhagen and Glostrup Hospital.

Other participants:

  • Professor Thomas Lars Andresen, Technical University of Denmark, DTU Nanotech, Department of Micro and Nanotechnology
  • Associate Professor Birger Brodin, University of Copenhagen, Faculty of Health and Medical Sciences, Department of Pharmacy, Pharmaceutical Design and Drug Delivery
  • Associate Professor Morten Schallburg Nielsen, Aarhus University, Health, Department of Biomedicine
  • Professor Torben Moos, Aalborg University, Faculty of Medicine, Department of Health Science and Technology
Researchers are searching for new ways to ‘smuggle’ medicine past the brain’s efficient defences. A new multidisciplinary research partnership involving DTU Nanotech is working to find ways to transport medicines across the blood-brain barrier. This barrier is a highly efficient ‘barricade’ that protects the brain, but also makes it difficult to treat conditions such as Alzheimer’s disease.

Fully 95 per cent of all pharmaceuticals tested for treating diseases of the brain fail because they cannot breach the blood-brain barrier. It is therefore essential to find possible paths past the brain’s ever vigilant checkpoint and committed protector. The Lundbeck Foundation has now brought together five of the brightest minds in Denmark to participate in a partnership intended to pinpoint innovative approaches to drug delivery and generate new knowledge about the brain’s ‘iron curtain’.

“Breaching the blood-brain barrier is a fundamental challenge in the development of new pharmaceuticals for treating diseases of the brain. The barrier is like an iron curtain created to protect the vulnerable brain, but it functions so efficiently that it is difficult to deliver pharmaceutical substances to treat conditions such as brain cancer, dementia or Parkinson’s. We are already familiar with a number of antibodies that should have a positive effect on Alzheimer’s, for example. The problem is to deliver them to the brain and then have them released in an appropriate manner,” explains Professor and neurophysiologist Martin Lauritzen from the University of Copenhagen and Glostrup Hospital, who is heading up the new Lundbeck Foundation Initiative on Brain Barriers and Drug Delivery.

In the new project, the researchers are coupling in vivo models—i.e. laboratory examinations of living brain tissue—with the very latest knowledge about pharmaceutical transport. Recent studies indicate that it is possible to connect a beneficial substance that the brain needs with a nanomolecule that can pass into the brain, and thus to ‘smuggle’ the pharmaceutical substance across the blood-brain barrier.

Blood-brain barrier tissue created in the laboratory using the new cultivation techniques can thus be used to see how the ‘smuggling operation’ functions in practice:

"The barrier is like an iron curtain created to protect the vulnerable brain, but it functions so efficiently that it is difficult to deliver pharmaceutical substances to treat conditions such as brain cancer, dementia or Parkinson’s. "
Professor and neurophysiologist Martin Lauritzen from the University of Copenhagen and Glostrup Hospital

“In the research group we have identified techniques for creating a very tight artificial blood-brain barrier. The laboratory-cultivated cell model is made by growing different types of brain cells under very special conditions. We can now use the model as a tool to ‘test drive’ the tricky route into the brain,” says Associate Professor Birger Brodin from the University of Copenhagen, who is a partner in the new multidisciplinary research project that has just been awarded a grant of DKK 40 million by the Lundbeck Foundation.

“If this project succeeds in transporting molecules into the brain as Trojan Horses, it will hold great potential for treatment of brain diseases. The Lundbeck Foundation is proud to support such an innovative and exciting project,” says Jørgen Huno Rasmussen, Chairman of the Board of the Foundation.

The blood-brain barrier is extremely complex and, like all living tissue, it develops dynamically. That is why it is also essential for the researchers to gain new knowledge about its physiological build-up, and about how it changes over time.

“There are small cracks in the barriers, through which molecules can access the brain. The problem—at least when you are trying to produce pharmaceuticals—is that they are quickly expelled again. The tissue material that the barrier comprises is constantly being renewed. We want to establish whether we can change the barrier properties so as to make it easier to transport medicines into the brain,” explains Martin Lauritzen.

The brain’s stronghold

The blood-brain barrier consists of a three-dimensional structure of blood vessels and support tissue that are positioned extremely close to each other, creating a physically tight barrier. It is also chemically tight, because the cells contain transport proteins which ensure that substances that enter the cells are immediately expelled into the blood once more. This is a problem when researchers are trying to design pharmaceuticals that act on the central nervous system.