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Treating stroke with Affibody molecules targeting the inflammatory mediator HMGB1

Objective

The scope of the project is to generate a candidate drug targeting the inflammatory mediator High mobility group box 1 protein (HMGB1) to be used in treatment of stroke. The candidate drug will be validated in animal models, characterized and optimized for subsequent clinical development.
Stroke remains a leading cause of death and disability throughout the world. Within EU, more than 500 000 persons die of stroke each year. Of those surviving stroke, 50% are left with physical or cognitive impairment and the total annual cost of stroke is estimated at Euro 27 billion.
Stroke occurs as a consequence of hemorrhagic insult or artery occlusion due to underlying cardiovascular disease. Pivotal in beneficial treatment of stroke is instant intervention. Blood clot dissolution using recombinant tissue plasminogen activator is the only pharmacological treatment demonstrated to limit neurological damage in stroke, but is only effective for patients who present within 3 hours after stroke onset. Thus there is an unmet need for an efficacious therapy that can be administered within and beyond 3 hours to achieve neuroprotection. HMGB1, released during the cerebral ischemic event and the subsequent neuroinflammation, is a well-characterized mediator of inflammation. Beneficial effects of blocking HMGB1 is proven in preclinical stroke studies. The drug to be developed is an Affibody molecule binding to and neutralizing HMGB1. Affibody molecules are engineered proteins significantly smaller than antibodies and therefore having favorable biodistribution properties, and a history of being efficient and non-toxic in clinical trials. In this application, we describe a multidisciplinary research consortium with Europe´s leading scientists in HMGB1 research and in registry-based clinical trial and dissemination methodology. The consortium has unique potentials to bring a new treatment principle against cerebral stroke to clinical reality.

Field of science

  • /medical and health sciences/basic medicine/neurology/stroke
  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins
  • /humanities/history and archaeology/history

Call for proposal

FP7-HEALTH-2013-INNOVATION-1
See other projects for this call

Funding Scheme

CP-FP - Small or medium-scale focused research project

Coordinator

KAROLINSKA INSTITUTET
Address
Nobels Vag 5
17177 Stockholm
Sweden
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 1 061 198,40
Administrative Contact
Caroline Hamilton (Mrs.)

Participants (5)

AFFIBODY AB
Sweden
EU contribution
€ 3 121 291
Address
Gunnar Asplunds Alle 24
171 63 Solna
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Fredrik Frejd (Prof.)
HMGBIOTECH SRL
Italy
EU contribution
€ 576 712
Address
Piazzale Gorini Paolo 8
20133 Milano
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Maura Casalgrandi (Dr.)
THE UNIVERSITY OF LIVERPOOL
United Kingdom
EU contribution
€ 396 562
Address
Brownlow Hill 765 Foundation Building
L69 7ZX Liverpool
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Daniel Antoine (Dr.)
UNIVERSITA VITA-SALUTE SAN RAFFAELE
Italy
EU contribution
€ 454 073,60
Address
Via Olgettina 58
20132 Milano
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Maria Rosa Pedrazzi (Dr.)
CHARITE - UNIVERSITAETSMEDIZIN BERLIN
Germany
EU contribution
€ 379 794
Address
Chariteplatz 1
10117 Berlin
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Karen Gertz (Dr.)