A new consortium of 27 international partners from academia, industry, and small and medium enterprises, aims to tackle the unmet challenge of discovery and characterisation of blood-brain barrier targets and transport mechanisms for brain delivery of therapeutics to treat neurodegenerative and metabolic diseases.
The new funding builds on previous research funded by the NIHR Oxford BRC into stem cell models of the blood-brain barrier (BBB).
The BBB is a protective layer between the brain’s blood vessels and the cells that make up brain tissue. This barrier provides a defence against the pathogens and toxins that may be in our blood, allowing very few molecules to pass through. It can also prevent many drugs from passing through into the brain, and this presents a major problem in treating neurological conditions and metabolic diseases, especially when using antibody therapies.
On the other hand, several neurological diseases could originate from a dysfunctional blood brain barrier.
The funding from the Innovative Medicines Initiative (IMI) to the IM2PACT consortium will allow this public-private partnership, which includes leading international experts in the field, to facilitate the development of drugs to treat neurological disorders by:
- discovering and developing innovative and effective brain transport mechanisms
- establishing and characterising BBB models with good predictability in health and disease
- identifying translational read-outs closer to the pathogenesis of neurodegeneration and mimicking altered BBB under disease conditions
- in-depth understanding of the biology of the BBB and characterisation of various pathophysiological mechanisms across the BBB
IM2PACT will foster the development of disease-modifying treatment in a setting of personalised medicine.
The project is coordinated by the Nuffield Department of Clinical Neurosciences (NDCN) at the University of Oxford. The Oxford team’s principal investigator and IM2PACT project coordinator, Zameel Cader, said: “With this funding, we will be able to develop more sophisticated models that replicate the human blood-brain barrier far more accurately, allowing us to investigate how the barrier acts at a molecular level during disease.”
Zameel Cader was the academic lead for the StemBANCC consortium, created in 2012 with funding from the IMI. This large group of European academic institutions and large pharma partners has developed a biorepository of induced pluripotent stem cell lines that are available for research use. Earlier research conducted by Zameel Cader’s team on stem cell models of the blood-brain barrier were funded by the NIHR Oxford BRC.
Dominique Lesuisse, Head of the Central Nervous System Barrier Group at Sanofi and IM2PACT project leader, added: “Our existing models are not effective enough at telling us which drugs in particular biotherapeutics will break through the blood-brain barrier. IM2PACT will progress the state of the art and help devise optimal ways of getting therapies into the brain.”
With a budget of €18m, €9m of direct funding from IMI and €9m of in-kind funding from industry, IM2PACT is forming a large partnership to better understand the blood-brain barrier. The Innovative Medicines Initiative 2 Joint Undertaking is Europe’s biggest public private partnership and is funded jointly by the European Union´s Horizon 2020 research and innovation programme and the European pharmaceutical industry, represented by the European Federation of Pharmaceutical Industries and Associations (EFPIA).