Abstract: The present invention relates to methods and composition for use in the treatment of retinal degeneration, in particular retinal degeneration due to retinal pigment epithelium dysfunction.

Abstract: Several new vector-promoter combinations to overcome the limitations associated with AAV-mediated cone transduction in the fovea are provided. The delivery modality relies on a cone-specific promoter and result in high-level transgene expression compatible with optogenetic vision restoration. Methods of expressing a polynucleotide of interest in the cone photoreceptors of a subject comprising subretinal delivery of a therapeutically effective amount of a recombinant AAV9-derived vector comprising a VP1 capsid protein as set forth in SEQ ID NO: 11 and the polynucleotide of interest under the control of the pR1.7 promoter as set forth in SEQ ID NO: 12 are also provided.

Abstract: The NXNL2 gene encodes by alternative splicing for a trophic factor RdCVF2 that enhances the function and the survival of neurons involved in long term memory. Now the inventors demonstrated that the cell surface receptor for the trophic factor RdCVF2 is NPTN65. The set-up of methods that could be used to screen for small molecules, agonists of RdCVF2 signaling in the brain would be suitable for the development of a future metabolic and redox treatment of tauopathies and in particular Alzheimer's disease.

Abstract: The present invention concerns a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound selected in the group comprising (i) a polypeptide comprising an amino acid sequence selected in the group comprising the amino acid sequence of the long isoform in Homo sapiens of the RdCVF2 gene (SEQ ID NO: 10), orthologs, derivatives and fragments thereof, (ii) a polynucleotide coding for said polypeptide, (iii) a vector comprising said polynucleotide, and (iv) a host cell genetically engineered expressing said polypeptide; the use of such a composition for the manufacture of a medicament for treating and/or preventing a neurodegenerative disorder in a subject; and a method of testing a subject thought to have or be predisposed to having a neurodegenerative disorder.

Abstract: The present invention concerns a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound selected in the group comprising (i) a polypeptide comprising an amino acid sequence selected in the group comprising the amino acid sequence of the long isoform in Homo sapiens of the RdCVF2 gene (SEQ ID NO: 10), orthologs, derivatives and fragments thereof, (ii) a polynucleotide coding for said polypeptide, (iii) a vector comprising said polynucleotide, and (iv) a host cell genetically engineered expressing said polypeptide; the use of such a composition for the manufacture of a medicament for treating and/or preventing a neurodegenerative disorder in a subject; and a method of testing a subject thought to have or be predisposed to having a neurodegenerative disorder.

Abstract: The invention relates to compounds which activate the BASIGIN signalling pathway, preferably agonists of BASIGIN, for the treatment of neurodegenerative disorders.

Abstract: The present invention relates to a new method for treating a patient suffering from a retinal degenerative disease. The Inventors discovered that nucleolin (NCL) is responsible in rods of the production of the short messenger of NXNL1 gene encoding RdCVF, a crucial factor for cones survival. Thus, the administration of NCL into the retina or the overexpression of NCL in recombinant cones to be transplanted into the retina, leads to a RdCVF expression and secretion by the cones themselves in order to encourage their own survival in an autocrine manner through the BSG1/GLUT1 complex. Thus, the invention concerns nucleolin polynucleotide or polypeptide for use in the treatment of a retinal degenerative disease in a patient in need. The invention also relates to recombinant cone overexpressing NCL for use in the treatment of a retinal degenerative disease.

Abstract: The present invention relates to an isolated nucleic acid molecule comprising i) a nucleotide sequence coding for a hyperpolarizing light-gated ion channel or pump gene from an archeon or for a light-active fragment of said gene, or the nucleotide sequence and ii) a nucleotide sequence coding for a neurotrophic factor for use in the treatment of a retinal degenerative disease.

Abstract: Several new vector-promoter combinations to overcome the limitations associated with AAV-mediated cone transduction in the fovea are provided. The delivery modality relies on a cone-specific promoter and result in high-level transgene expression compatible with optogenetic vision restoration. Methods of expressing a polynucleotide of interest in the cone photoreceptors of a subject comprising subretinal delivery of a therapeutically effective amount of a recombinant AAV9-derived vector comprising a VP1 capsid protein as set forth in SEQ ID NO: 11 and the polynucleotide of interest under the control of the pR1.7 promoter as set forth in SEQ ID NO: 12 are also provided.

Abstract: The invention relates to the use of HNRNPC-expressing vectors for preventing and/or treating a tauopathy, such as Alzheimer's disease. The invention relates to methods for detecting a risk of developing a tauopathy such Alzheimer's disease in a patient, comprising the step of detecting the level of HNRNPC in a biological sample obtained from said patient.

Abstract: The invention relates to the use of HNRNPC-expressing vectors for preventing and/or treating a tauopathy, such as Alzheimer's disease. The invention relates to methods for detecting a risk of developing a tauopathy such Alzheimer's disease in a patient, comprising the step of detecting the level of HNRNPC in a biological sample obtained from said patient.

Abstract: The present invention relates to improved constructs comprising the short and long Rod-Derived Cone Viability Factors and to methods for treating retinal degenerative diseases.

Abstract: The present invention concerns a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound selected in the group comprising (i) a polypeptide comprising an amino acid sequence selected in the group comprising the amino acid sequence of the long isoform in Homo sapiens of the RdCVF2 gene (SEQ ID NO: 10), orthologs, derivatives and fragments thereof, (ii) a polynucleotide coding for said polypeptide, (iii) a vector comprising said polynucleotide, and (iv) a host cell genetically engineered expressing said polypeptide; the use of such a composition for the manufacture of a medicament for treating and/or preventing a neurodegenerative disorder in a subject; and a method of testing a subject thought to have or be predisposed to having a neurodegenerative disorder.

Abstract: The present invention relates to the synergistic combination of the short and long Rod-Derived Cone Viability Factors and to methods for treating retinal degenerative diseases.

Abstract: The present invention relates to methods and pharmaceutical compositions for the treatment of retinal degenerative diseases. The inventors identified a new key actor of the mechanism underlying the protective role of RdCVF: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 (PFKFB2). The inventors showed that PFKFB2 is expressed by cones in a rod-dependant manner. In particular, they showed that its expression follows the viability of cones: its expression is lost in an animal model retinitis pigmentosa. The inventors accumulated evidences that PFKFB2, especially its kinase domain, is involved in the mechanism of action of RdCVF. More particularly they showed that transduction of a polynucleotide encoding for PFKFB2 increases cone survival. In particular, the present invention relates to a method of treating a retinal degenerative disease in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a polynucleotide encoding for the PFKFB2 kinase domain.

Abstract: The present invention concerns a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound selected in the group comprising (i) a polypeptide comprising an amino acid sequence selected in the group comprising the amino acid sequence of the long isoform in Homo sapiens of the RdCVF2 gene (SEQ ID NO: 10), orthologs, derivatives and fragments thereof, (ii) a polynucleotide coding for said polypeptide, (iii) a vector comprising said polynucleotide, and (iv) a host cell genetically engineered expressing said polypeptide; the use of such a composition for the manufacture of a medicament for treating and/or preventing a neurodegenerative disorder in a subject; and a method of testing a subject thought to have or be predisposed to having a neurodegenerative disorder.

Abstract: The invention relates to the use of HNRNPC-expressing vectors for preventing and/or treating a tauopathy, such as Alzheimer's disease. The invention relates to methods for detecting a risk of developing a tauopathy such Alzheimer's disease in a patient, comprising the step of detecting the level of HNRNPC in a biological sample obtained from said patient.

Abstract: The present invention relates to methods and pharmaceutical compositions for the treatment of age-related macular degeneration (AMD). In particular the present invention relates to RdCVFL polypeptide or polynucleotide for use in the treatment of AMD.

Abstract: The present invention relates to the synergistic combination of the short and long Rod-Derived Cone Viability Factors and to methods for treating retinal degenerative diseases.

Abstract: The present invention relates to methods and composition for use in the treatment of retinal degeneration, in particular retinal degeneration due to retinal pigment epithelium dysfunction.