Centre National De La Recherche Scientifique

Genethon

National Institute of Health and Medical Research

Université Pierre Et Marie Curie (Paris 6)

Association Institut De Myologie

Aventis Pharma S.a.

Sorbonne Université

Université Pierre Et Marie Curie

Martine Barkats

Jacques Mallet

Thomas Voit

Frédéric Revah

Maria-Grazia Biferi

Stéphanie Millecamps-Navarro

The present invention relates to compositions and methods for the delivery of therapeutic proteins to the CNS using recombinant AAV vectors. More specifically, the invention relates to compositions and methods for delivering proteins into the cerebrospinal fluid of mammalian subjects through peripheral administration of AAV vectors. The invention may be used to treat various disorders of the central nervous system, including degenerative diseases and motor neuron diseases.

CNS gene delivery using peripheral administration of AAV vectors

The present invention relates to compositions and methods, in particular to methods based on systemic injection of rAAV, for delivering genes to cells of the central nervous system in mammals, such as brain neurons or glial cells, and in particular to motor neurons or glial cells of the spinal cord The invention also relates to methods of treating motor neuron disorders in mammals by expression of therapeutic genes. The invention stems from the unexpected discovery that peripheral injection of AAV vectors leads to a bypass of the blood brain barrier and a massive infection of motor neurons. The invention may be used in any mammal, including human subjects.

Widespread gene delivery to motor neurons using peripheral injection of AAV vectors

The invention relates to a method for the treatment of amyotrophic lateral sclerosis (ALS). Specifically, the invention implements the use of an antisense sequence adapted to affect alternative splicing in a human SOD1 pre-mRNA, thereby leading to the destruction of the skipped m RNA by the cell machinery.

Treatment of amyotrophic lateral sclerosis

The present invention relates to compositions and methods, in particular to methods based on systemic administration of scAAV, for delivering genes to cells of the retina of mammals, and in particular to photoreceptor cells, ganglion cells, glial cells, inner nuclear layer cells or cells of the retinal pigmented epithelium.

Widespread gene delivery to the retina using systemic administration of AAV vectors

The present invention is related to compositions and methods for the delivery of nucleic acids to neurons in a mammal, and uses thereof. The present invention specifically discloses the use of compounds that cause synaptic nerve sprouting to increase neuron retrograde transport of a vector or a product (a polypeptide or a nucleic acid for example) in a mammal. The invention is also based on the use of a compound that interacts with synaptosomal associated proteins to increase neuron retrograde transport of a vector or a product such as one cited above in a mammal. The invention also relates to a product comprising a viral vector comprising a transgene and a compound that causes synaptic nerve sprouting, for sequential use for delivering said transgene to neurons by retrograde transport and its uses for the preparation of a composition used as a treatment in several neurological disorders. The methods and compositions of this invention can be used to deliver various transgenes, such as markers, vaccines, therapeutic genes etc., and are suitable for experimental, therapeutic or various other applications.

Neuronal gene transfer of adenovirus and herpes virus vectors

The present invention relates to a defective adenovirus comprising at least a DNA sequence coding for all or an active part of glutathione peroxidase or a derivative thereof. It also relates to their utilization in therapy and to the corresponding pharmaceutical compositions.

Growing community of inventors

Charenton le Pont, France

Martine Barkats