nathalie cartier-lacave MD, Gene therapy for neurodegenerative diseases

Course and current status


Research Director Exceptional class (DRCE) Biotherapy group at MIRCen CEA (INSERM/CEA UMR 1169)



1992 : Medical Doctor, University Paris Descartes; Internship Hôpitaux de Paris; specialized in Pediatrics


Research and Professional Experience

1990-1993: associate researcher at INSERM

1995: Full time researcher at INSERM

2000: Director of research at INSERM

2010: First class Research Director at INSERM

2016 : Exceptional class Research Director at INSERM


1990-2014 : medical consultant Endocrinology/ Neuropediatry unit (Saint Vincent de Paul Hospital)


Teaching activity

 Associate Professor at University Paris Descartes : biotherapies and medical semiology     (2010-2013)

Co-Direction of the post graduate course : inter-university diploma (DIU) : translational      research in neurosciences Paris Sud universsity/UPMC (2013-2016) 

Direction of the pre-PhD course : Biotherapy course of the Magistere of Genetics, Paris       Descarte/paris Diderot universities)- (2007-current)

Co-direction  of The  European  Spring Schools  in Biotherapies  (2014-current)


Participation to 5 master courses and Medical courses : Genetics, Neurosciences, Biotherapies  (20 hours per year)


Main domains of research:

Development of gene therapy applications for neurodegenerative diseases , from genetic leukodystrophies to Alzheimer disease, Huntington disease, spinocerebellar ataxias. Work includes all translation steps from preclinical proof of concept in animal models to clinical application in human patients : vector development, characterization  of animal models, gene transfer and evaluation in animal models, submission  of clinical application to regulatory agencies, clinical trials.

Co-PI in gene therapy clinical trials for Adrenoleukodystrophy (2006) and metachromatic leukodystrophy (current)


Research Grants

- National Research grants (ANR 2008 and ANR France-Canada 2010-2013): Research on        Alzheimer’s Disease and Related Disorders (partner)

- Research grants from French associations ELA (2000-2009; 2017-2019), Fondation de            l’Avenir (2007-2009), AFM (2000-2009) on gene therapy for X-adrenoleukodystrophy     and metachromatic leukodystrophy(coordinator)

- EU-FP6 project 2004-2008 (Adrenoleukodystrophy) (partner)

- FP7-HEALTH-2009-2012. LeukoTreat (partner)

- Clinigene European consortium on Gene Therapy (2008) (partner)

- European ERAnet project on Alzheimer disease (2013-2016) (partner)

- ANR project Stemimus on myelin repair and hematopoitic stem cells (partner 220 000€)

- Optogenerapy H2020 program (2017-2020) (partner; 550 000€)

- Bioingenierie pour la santé (Fondation pour la recherché Médicale; 2015-2018)       (coordinator; 400 000€ )

- ANR HDCYP (PCRI 2017-2019) (coordinator ; 352 000€)

- ELA grant on remyelination (2017-2019) (coordinator; 120 000€)

- Maturation program from the SATT Ile de France Innov (Société d’accélération de Transfert         Technologique) 2016-2018 (coordinator; 400 000 €)


National expertise

Member of the INSERM clinical research evaluation committee (CSS8) 2006 – 2012)

Member of the COSSEC (comity for organization and follow-up of clinical trials in cell and gene therapy) (2007 – current)

Member of the scientific committee of the Association Francaise contre les Myopathies     (AFM) (2010-current )

Coordinator of the DIM biotherapy (French Governmental Network for stem cell, cell and    gene therapy research ; 180 academic teams, 1,2Million€/year) (2011-2016)

Vice President of the the scientific committee of the Fondation Jerome Lejeune (2012-2014)

Member of the Scientific Committee of INSERM (2012- 2017)

Vice President (2012) and President (since 2017) of the the scientific committee of the         Fondation Maladies Rares


European expertise

Member of the Gene Therapy Working Party (GTWP) European Medicine Agency (EMA)

Member of the scientific committee of the Janssen  research fund (2017)

Member of the scientific committe of the Hanover Medical School (2015-current)


Memberships and activity in Professional Societies

Member of the educational committee of the  American Society for Cell and Gene Therapy             (2003 – current)

Vice-President (2012-2014) then President (2014-2016) of the European Society for Cell and Gene Therapy

2011 - 2015 : President of the French Society for Gene Therapy

Member (corresponding) of the  French National Academy of Medicine (section biology)     since 2012



Jean Valade award  (Fondation de France) (2004)

Thermo Biotherapie award (2007)

Sisley-Lejeune award (2010)

Drieu – Cholet (Académie de Médecine)  award (2010)

Chevalier de la Légion d’Honneur  (French Government award) (2010)

Mémain-Pelletier de l’Académie des Sciences award (2011)

Corresponding member of the French Academy of Medicine (2012)

Scientific summary


My work is dedicated to the development of gene therapy strategies for neurodegenerative diseases, from identifying and validating therapeutic targets to demonstrating preclinical feasibility and tolerance in rodents, translating to large animals (primates) and finally to therapeutic trials. My initial work led to two Gene Therapy clinical trials for Adrenoleukodystrophy (first trial using HIV vector to correct hematopoietic cells, Science 2009), and Metachromatic Leukodystrophy (AAV delivery to the brain). I am co-PI of these trials.

My team (12 persons) individualized from UMR1169 INSERM is located at MIRCen (Molecular Imaging Center) CEA since end of 2012 to benefit from specific infrastructures to develop translational research. Long-lasting close collaborations have been established with ICM teams on both preclinical and clinical programs (A Durr, C Lubetzki, C Dyuckaerts).

Our current work is mainly devoted to Alzheimer’s disease (AD) and Huntington’s disease (HD). We have demonstrated the role of cerebral cholesterol homeostasis and of cholesterol 24 hydroxylase enzyme  (CYP46A1) in these pathologies (Djelti, 2015; Boussicault, 2015). CYP46A1 delivery through the injection of AAV-CYP46A1 vector in brain regions affected by the diseases correct the whole clinical, biochemical and neuropathological phenotype of several murine models of AD and HD (Hudry 2010, Burlot, 2015, Boussicault 2015), confirming the relevance of this therapeutic strategy in these severe neurodegenerative conditions with no therapeutic option. Our current work in non-human primates demonstrate the feasibility and the tolerance of this approach (diffusion, dose-response, biomarker) towards a clinical application in human patients. Our location at MIRCen and collaboration with P Hantraye allow the development of this crucial step. I have secured financial supports (FRM, SATT IDF INNOV, ANR PCRI with BrainVectis Therapeutics) and  developed the specific clinical network  towards submission of a clinical application to the ANSM and EMA.

Our other programs concern

1)     the evaluation of therapeutic targets for MA : APPs alpha et Il2. Our results confirm their beneficial role (Fol Acta neuropath 2015, Fol en préparation, Alves Brain 2017, patent application EP15305904.3). National (D KLatzmann ; clinical trial in preparation with B Dubois ICM) and  international collaboration are ongoing to further develop these programs  (Harvard A Biffi).

2)     Remyelination in demyelinating disorders HSC transplantation allows the reconstitution of brain microglial cells and is an effective therapeutic strategy (Cartier 2009, Cartier 2014). These cells can be genetically modified ex vivo and reconstitute microglia to deliver therapeutic proteins to the brain. We used this strategy to express Sema3F in microglia, a molecule inducing the recruitment of oligodendrocytes progenitors in induced demyelinating lesions. This is tested for multiple sclerosis (MS). Same strategy will be extended to leukodystrophies, particularly MLD (C Sevin). The kinetics of microglia reconstitution after transplantation is under evaluation thanks to a transnational program financed by Bluebird Bio, involving Pasteur (PM Lledo), Heidelberg DKFZ (B Tews, C von Kalle) and our team. 

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