M. Barkats group
M. Barkats group : Gene therapy for CNS and motor neuron diseases
Références :
(1) Patent N°EP07301535.9 (Oct 2007) Europe. GENETHON/CNRS. Widespread gene delivery to motor neurons using peripheral injection of AAV vectors. Inventor: Martine Barkats.
(2) S. Duque, et al. (2009) : Intravenous Administration of Self-Complementary AAV 9 Enables Transgene Delivery to Adult Motor Neurons. Mol Ther. 17(7):1187-96
(3) E. Dominguez, et al. : Intravenous injection of SMN1-expressing self-complementary AAV9 rescues severe type I SMA mice (Submitted).
- Spinal muscular atrophy
- SMN1 gene transfer : We recently demonstrated the remarkable efficiency of an AAV (adeno-associated virus)-derived vector, the self-complementary AAV9 (also termed double-stranded AAV9), for gene transfer into cells of the central nervous system (CNS) including the spinal motor neurons. This new approach is based on the single injection of the scAAV9 vector into the circulation, this vector displaying the remarkable ability to cross the blood-brain barrier (Refs 1,2).
We also provided evidence of the therapeutic efficacy of this new technology in a mouse model of SMA after intravenous injection of a scAAV9 expressing the human SMN1 gene in SMNdelta7 mice (Ref 3).
This research will soon lead to the initiation of a preclinical study in non-human primates in order to prepare a possible clinical application in patients with SMA. This new method of gene transfer might be promising for the development of gene therapy for SMA but also for many disorders of the central and peripheral nervous system.
- Exon 7 inclusion : We are also working, in collaboration with Daniel Schümperli (Lausanne), on a therapeutic approach based on exon 7 inclusion in the SMN2 gene, using intravenous injection of scAAV9 encoding a SMN2-specific bi-functional U7 RNA in SMNdelta7 mice.
We also provided evidence of the therapeutic efficacy of this new technology in a mouse model of SMA after intravenous injection of a scAAV9 expressing the human SMN1 gene in SMNdelta7 mice (Ref 3).
This research will soon lead to the initiation of a preclinical study in non-human primates in order to prepare a possible clinical application in patients with SMA. This new method of gene transfer might be promising for the development of gene therapy for SMA but also for many disorders of the central and peripheral nervous system.
- Exon 7 inclusion : We are also working, in collaboration with Daniel Schümperli (Lausanne), on a therapeutic approach based on exon 7 inclusion in the SMN2 gene, using intravenous injection of scAAV9 encoding a SMN2-specific bi-functional U7 RNA in SMNdelta7 mice.
- Functional genetics : In collaboration with Louis Viollet (Paris), we are also interested in the functional study of newly identified genes involved in "atypical" SMA (excluded from the SMN locus) (Maystadt I et al, Am J Hum Genet. 2007; Astord S.*, Blumen S.C.* et al., submitted)
- Other projects
- Modelling and systemic gene therapy of ALS (collaboration with Jean-Philippe Loeffler, Strasbourg)
- Systemic gene therapy of retina diseases (collaboration with Alexis Bemelmans and José Sahel, Paris).
- Gene therapy for lysosomal storage disorders (collaborations with (1) Catherine Caillaux, Paris (2) Beatrice Joussemet, Nantes)
- Gene Therapy of Rett syndrome (collaboration with Jean-Christophe Roux and Nicolas Lévy, Marseille).
- Modelling and gene therapy for spinocerebellar ataxia (Collaboration with Giovanni Stevanin, Annie Sittler, Alexis Brice and coll., Paris).
- Systemic gene therapy of retina diseases (collaboration with Alexis Bemelmans and José Sahel, Paris).
- Gene therapy for lysosomal storage disorders (collaborations with (1) Catherine Caillaux, Paris (2) Beatrice Joussemet, Nantes)
- Gene Therapy of Rett syndrome (collaboration with Jean-Christophe Roux and Nicolas Lévy, Marseille).
- Modelling and gene therapy for spinocerebellar ataxia (Collaboration with Giovanni Stevanin, Annie Sittler, Alexis Brice and coll., Paris).
Références :
(1) Patent N°EP07301535.9 (Oct 2007) Europe. GENETHON/CNRS. Widespread gene delivery to motor neurons using peripheral injection of AAV vectors. Inventor: Martine Barkats.
(2) S. Duque, et al. (2009) : Intravenous Administration of Self-Complementary AAV 9 Enables Transgene Delivery to Adult Motor Neurons. Mol Ther. 17(7):1187-96
(3) E. Dominguez, et al. : Intravenous injection of SMN1-expressing self-complementary AAV9 rescues severe type I SMA mice (Submitted).
Update: April 2010
