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Repurposing of carbamazepine for treatment of skeletal dysplasia

Objective

Genetic skeletal diseases (GSDs) are an extremely diverse and complex group of rare genetic diseases that affect the development the skeleton. There are more than 450 unique and well-characterised phenotypes that range in severity from relatively mild to severe and lethal forms. Although individually rare, as a group of related genetic skeletal diseases, GSDs have an overall prevalence of at least 1 per 4,000 children, which extrapolates to a minimum of 225,000 people in the 27 member states and candidate countries of the EU. This burden in pain and disability leads to poor quality of life and high healthcare costs.
Metaphyseal chondrodysplasia, type Schmid (MCDS) results from mutations in collagen X and affects <1/100,000 of the population. Mutant collagen X molecules miss-fold during synthesis and are retained within the endoplasmic reticulum (ER) of hypertrophic chondrocytes, thereby causing ER stress. Our extensive pre-clinical studies have shown that carbamazepine (CBZ) can alleviate ER stress caused by the expression of mutant collagen X and restore bone growth in a validated mouse model of MCDS. CBZ is an FDA approved drug used for the treatment of epilepsy and bipolar disorder and received orphan drug designation by the European Commission for the treatment of MCDS in September 2016.
MCDS-Therapy is a 5-year collaborative project comprising world-renown clinical centres and SMEs to advance the repurposing of CBZ for MCDS (up to the Marketing Authorization Application dossier) through a multicentre and multinational (EU & AUS) clinical trial (Phase1, Phase2/3). MCDS-Therapy also encompasses biomarker development and health economics assessment studies to deliver by 2022 an innovative and affordable (CBZ already exists in a generic form) repurposed therapy for MCDS along with the diagnosis/prognosis tools to personalise the treatment strategy.

Field of science

  • /social sciences/economics and business/economics
  • /natural sciences/biological sciences/genetics and heredity/mutation
  • /medical and health sciences/basic medicine/neurology/epilepsy
  • /social sciences/economics and business

Call for proposal

H2020-SC1-2017-Two-Stage-RTD
See other projects for this call

Funding Scheme

RIA - Research and Innovation action

Coordinator

UNIVERSITY OF NEWCASTLE UPON TYNE
Address
Kings Gate
NE1 7RU Newcastle Upon Tyne
United Kingdom
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 2 175 161,25

Participants (9)

ASSISTANCE PUBLIQUE HOPITAUX DE PARIS
France
EU contribution
€ 211 479
Address
3 Avenue Victoria
75000 Paris
Activity type
Research Organisations
UNIVERSITAIR ZIEKENHUIS ANTWERPEN
Belgium
EU contribution
€ 120 750
Address
Wilrijkstraat 10
2650 Edegem
Activity type
Research Organisations
UNIVERSITAETSKLINIKUM FREIBURG
Germany
EU contribution
€ 657 569
Address
Hugstetter Strasse 49
79106 Freiburg
Activity type
Higher or Secondary Education Establishments
MURDOCH CHILDRENS RESEARCH INSTITUTE
Australia
EU contribution
€ 318 625
Address
Flemington Road Rch
3052 Parkville
Activity type
Research Organisations
GUYS AND ST THOMAS' NHS FOUNDATIONTRUST
United Kingdom
EU contribution
€ 197 428,75
Address
Westminster Bridge Road
SE1 7EH London
Activity type
Research Organisations
FINDACURE FOUNDATION
United Kingdom
EU contribution
€ 309 235
Address
66 Devonshire Road
CB1 2BL Cambridge
Activity type
Research Organisations
ISTITUTO ORTOPEDICO RIZZOLI
Italy
EU contribution
€ 782 175
Address
Via Di Barbiano 1/10
40136 Bologna
Activity type
Research Organisations
SCIOMICS GMBH
Germany
EU contribution
€ 604 030
Address
Schneidmuhlstrasse 19
69115 Heidelberg
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
FINOVATIS
France
EU contribution
€ 320 937,50
Address
Cours Lafayette 68
69003 Lyon
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)