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Adeno-Associated Virus Vector-Mediated Liver Gene Therapy for Crigler-Najjar Syndrome

Objective

Crigler-Najjar syndrome (CN) is a rare recessive disorder caused by mutations in the uridine diphosphate glucuronosyltransferase 1A1(UGT1A1) gene. CN is a life-threatening disease with no cure which constitutes a severe burden for the patients, their families, and the society. CureCN has the objective of developing a curative gene therapy for CN syndrome based on liver gene transfer with and adeno-associated virus (AAV) vector expressing the UGT1A1 transgene. Additional goals of CureCN are to develop strategies to allow for vector re-administration and to address the issue of pre-existing anti-AAV neutralizing antibodies (NAbs), which prevent large proportion of seropositive patients from receiving AAV mediated gene therapy. Proof-of-concept studies of AAV8-UGT1A1 gene transfer provide a strong rationale for the safety and efficacy of gene therapy for CN. CureCN proposes to carry out an open-label, multicenter clinical trial of AAV8-UGT1A1 gene transfer to prove the safety and efficacy of the therapy in severe CN patients, and file for marketing authorization in Europe at the end of the study. CureCN will also produce enabling data for the clinical translation of a groundbreaking immunomodulatory strategy to allow for vector administration. Additionally, a technology for the selective removal of anti-AAV NAbs from the bloodstream of seropositive patients will be developed. The goal of these studies is to ultimately allow all CN patients to access AAV8-UGT1A1 gene therapy. CureCN is a patient-driven initiative that gathers top clinicians and scientists; it also includes small medium enterprises in its partners, to foster economic growth and valorization of intellectual property. CureCN sets itself in the ambitious goal set by the IRDiRC by 2020 by developing a curative treatment for CN syndrome. Importantly, it validates technologies that will broaden the scope of gene therapy, thus will have an impact on the development of treatments for several other rare diseases.

Field of science

  • /natural sciences/biological sciences/genetics and heredity/mutation
  • /medical and health sciences/medical biotechnology/genetic engineering/gene therapy

Call for proposal

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

Funding Scheme

RIA - Research and Innovation action

Coordinator

ASSOCIATION GENETHON
Address
Rue De L Internationale 1 Bis
91002 Evry
France
Activity type
Research Organisations
EU contribution
€ 3 738 478,75

Participants (10)

ASSISTANCE PUBLIQUE HOPITAUX DE PARIS
France
EU contribution
€ 172 083,75
Address
3 Avenue Victoria
75000 Paris
Activity type
Research Organisations
ACADEMISCH MEDISCH CENTRUM BIJ DE UNIVERSITEIT VAN AMSTERDAM
Netherlands
EU contribution
€ 526 718,75
Address
Meibergdreef 15
1105AZ Amsterdam
Activity type
Higher or Secondary Education Establishments
MEDIZINISCHE HOCHSCHULE HANNOVER
Germany
EU contribution
€ 149 000
Address
Carl-neuberg-strasse 1
30625 Hannover
Activity type
Higher or Secondary Education Establishments
AZIENDA OSPEDALIERA PAPA GIOVANNI XXIII
Italy
EU contribution
€ 147 500
Address
Piazza Oms 1
24127 Bergamo
Activity type
Other
UNIVERSITA DEGLI STUDI DI NAPOLI FEDERICO II
Italy
EU contribution
€ 147 125
Address
Corso Umberto I, 40
80138 Napoli
Activity type
Higher or Secondary Education Establishments
GENOSAFE SAS
France
EU contribution
€ 207 017,50
Address
Rue De L'internationale 1
91000 Evry
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
ASSOCIATION FRANCAISE DE CRIGLER NAJJAR
France
EU contribution
€ 92 000
Address
8 Rue Henri Golaudin
92140 Clamart
Activity type
Other
MC TOXICOLOGY CONSULTING GMBH
Austria
EU contribution
€ 156 872,50
Address
Siebensterngasse 31/8
1070 Wien
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
UNIVERSITY OF LEICESTER
United Kingdom
EU contribution
€ 396 182,50
Address
University Road
LE1 7RH Leicester
Activity type
Higher or Secondary Education Establishments
EURICE EUROPEAN RESEARCH AND PROJECT OFFICE GMBH
Germany
EU contribution
€ 516 125
Address
Heinrich-hertz-allee 1
66386 St Ingbert
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)