Objective Lentiviral vectors pseudotyped with the rabies-G envelope have been used for the delivery of therapeutic transgenes via the peripheral intamuscular route, increasing lifespan and reducing neuromuscular deficits in mouse models of both amyotrophic lateral sclerosis and spinal muscular atrophy. Despite these successes clinical translation of gene therapy for ALS with these and other vectors with retrograde transport such as AAV2 has been hampered as a result of limitations experienced with gene transfer in non-human primates (NHPs). In order to overcome these limitations, and to design a safe, efficient and a minimally invasive therapeutic strategy, we have developed as part of the ERC Advanced investigator’s grant: IRLVGTMND, a novel new generation of surface engineered lentiviral vectors with tropism to motor neurons (MNs) via the neuromuscular junction (NMJ). These vectors are targeted with antibodies against NMJ presynaptic terminal receptors, such as the CAR (coxsackievirus and adenovirus receptor). We found that these vectors can recognise, bind and enter target cells with high specificity determined by the antibody incorporated on their surface. They have specificity for MNs and have retrograde transport as demonstrated in vitro in compartmentalised primary motor cultures and in vivo upon intramuscular (i.m.) delivery in leg muscles leading to transduction of lumbar spinal cord MNs. All data to date indicate that the targeted lentiviral vectors we have constructed have superior transduction and specificity for MNs than previously used lentiviral vectors, making them thus good candidates for minimally invasive neuroprotective gene therapy of ALS. We therefore with this PoC grant want to investigate the transduction of NHP MNs via i.m. injections. We aim to have an indication within 12 months whether these vectors can achieve sufficient transduction in this model which will open up the way for their preclinical development, clinical testing and commercialisa Fields of science natural sciencesbiological scienceszoologymammalogyprimatologymedical and health sciencesmedical biotechnologygenetic engineeringgene therapymedical and health sciencesbasic medicineneurologyamyotrophic lateral sclerosis Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) ERC-OA-2013-PoC - European Research Council ERC Proof of Concept Call for proposal ERC-2013-PoC See other projects for this call Funding Scheme CSA-SA(POC) - Supporting action (Proof of Concept) Host institution IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE EU contribution € 110 302,98 Address SOUTH KENSINGTON CAMPUS EXHIBITION ROAD SW7 2AZ LONDON United Kingdom See on map Region London Inner London — West Westminster Activity type Higher or Secondary Education Establishments Administrative Contact Tatjana Palalic (Ms.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data Beneficiaries (2) Sort alphabetically Sort by EU Contribution Expand all Collapse all IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE United Kingdom EU contribution € 110 302,98 Address SOUTH KENSINGTON CAMPUS EXHIBITION ROAD SW7 2AZ LONDON See on map Region London Inner London — West Westminster Activity type Higher or Secondary Education Establishments Administrative Contact Tatjana Palalic (Ms.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data ASSISTANCE PUBLIQUE HOPITAUX DE PARIS France EU contribution € 39 223,00 Address 55 BOULEVARD DIDEROT 75012 Paris See on map Region Ile-de-France Ile-de-France Val-de-Marne Activity type Research Organisations Administrative Contact Alix Pillot (Ms.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
