Institut National De La Sante Et De La Recherche Medicale

Assistance Publique-hopitaux De Paris

Centre National De La Recherche Scientifique

Université Paris Descartes

Assistance Publique - Hopitaux De Paris (aphp)

Universite Paris Cité

Fondation Imagine

Imagine

Other

Ipsen Pharma S.a.s.

Université Paris Diderot-paris 7

Université De Paris

Genethon

Inserm (institut National De La Sante Et De La Recherche Medicale)

Apotex Technologies Inc.

Arnold Munnich

Daniel Scherman

Michael Spino

Laurence Legeai-Mallet

Richard A Lewis

Antoine Kichler

Judith Melki

Florent Barbault

Patricia Busca

Annemarie Poustka

Josseline Kaplan

Isabelle Perrault

Xavier Gerard

Jean-Michel Rozet

Alain Israel

David L Nelson

François Clostre

Mehemed Ouzid

Hayley Woffendin

Sue J Kenwrick

Nina Heiss

Michele D'Urso

Valerie Cormier-Daire

Asmae Smahi

Swaroop Aradhya

Moise Levy

Sylvain Hanein

Anne Agnès Rotig

Floriane Petit

Valérie Cormier-Daire

Ioav Cabantchik

Sylvie Gerber

Friedreich ataxia (FRDA) is caused by a GAA repeat expansion in FXN gene that encodes a mitochondrial protein, frataxin, involved in iron sulfur complex (ISC) assembly. Frataxin deficiency results in abnormal ISC containing proteins, namely respiratory chain complex I-III and aconitases and accumulation of iron in brain and heart of patients. Here, the inventors show that FRDA fibroblasts are unable to limit iron uptake inducing a massive cytosolic iron accumulation and to a lesser extent in mitochondria. The inventors also observed increased transferrin receptor (TfR1) steady state levels and membrane TfR1 accumulation that they ascribed to impaired post-translational modification by palmitoylation as well as delayed transferrin recycling. Finally, the inventors showed that artesunate, dichloroacetate and Coenzyme-A improved TfR1 palmitoylation and thus represent candidate molecules for the treatment of patients with Friedreich ataxia. Thus the present invention relates to methods of treating Friedreich ataxia (FRDA) as well as to methods of predicting whether a patient suffering from FRDA will achieve a therapeutic response.

Treatment and prediction of therapeutic responses in patients suffering from Friedreich ataxia

The present invention relates to methods for performing antisense oligonucleotide-mediated exon skipping in the retina of a subject in need thereof. In particular, the present invention relates to a method for performing antisense oligonucleotide-mediated exon skipping in a retina cell of a subject comprising the step of injecting into the vitreous of the subject an amount of the antisense oligonucleotide.

Methods for performing antisense oligonucleotide-mediated exon skipping in the retina of a subject in need thereof

The present invention relates to the treatment or prevention of skeletal disorders, at particular skeletal diseases, developed by patients that display abnormal increased activation of the fibroblast growth factor receptor 3 (FGFR3), in particular by expression of a constitutively activated mutant of FGFR3.

Antagonist of the fibroblast growth factor receptor 3 (FGFR3) for use in the treatment or the prevention of skeletal disorders linked with abnormal activation of FGFR3

The present invention relates to the treatment or prevention of skeletal disorders, in particular skeletal diseases, developed by patients that display abnormal increased activation of the fibroblast growth factor receptor 3 (FGFR3), in particular by expression of a constitutively activated mutant of FGFR3.

Described herein are methods of the treatment and diagnosis of bone mineral density related disorders. More particularly, described herein are methods of diagnosing or predicting a bone mineral density related disease, or a risk of a bone mineral density related disease, in a subject, which method comprises detecting a mutation in the TBXAS1 gene, wherein the presence of such a mutation is indicative of a bone mineral density related disease or of a risk of a bone mineral density related disease. Also described are compounds such as a thromboxane synthase (TXAS) encoding polynucleotide, a TXAS, thromboxane A2 or an analog thereof for treating or preventing a disease associated with an increased bone mineral density (e.g., Ghosal hematodiaphyseal dysplasia syndrome). Additional aspects describe an inhibitor of TBXAS1 gene expression or a thromboxane inhibitor for treating or preventing a disease associated with a decreased bone mineral density (e.g., osteoporosis).

Methods for the treatment and diagnosis of bone mineral density related diseases

The present invention relates to the discovery of the human survival motor-neuron gene or SMD gene, which is a chromosome 5-SMA (Spinal Muscular Atrophy) determining gene. The present invention further relates to the nucleotide sequence encoding the SMN gene and corresponding amino acid sequence, a vector containing the gene encoding the SMN protein or a DNA sequence corresponding to the gene and transformant strains containing the SMN gene or a DNA sequence corresponding to the gene.

Spinal muscular atrophy diagnostic methods

Survival motor neurons (SMN) gene: a gene for spinal muscular atrophy

The invention relates to the use offor the treatment of mitochondrial diseases of genetic origin and more particularly mitochondrial encephalomyopathies.

[object Object]

Incontinentia Pigmenti (IP) is a neurocutaneous genodermatosis that segregates as an X-linked dominant disorder with a high probability of prenatal male lethality. A locus in Xq28 containing NF-&kgr;B Essential Modulator, a gene product involved in the activation of NF-kB and central to many pro-inflammatory and apoptotic pathways, contains mutations in the majority of cases of IP. Disclosed are methods, compositions and kits directed to a defect in a NF-&kgr;B related disease such as IP.

Diagnosis and treatment of medical conditions associated with defective NFkappa B(NF-&kgr;B) activation

The present invention relates to the discovery of the human survival motor-neuron gene or SMN gene which is a chromosome 5-SMA (Spinal Muscular Atrophy) determining gene. The present invention further relates to the nucleotide sequence encoding the SMN gene and corresponding amino acid sequence, a vector containing the gene encoding the SMN protein or a DNA sequence corresponding to the gene and transformant strains containing the SMN gene or a DNA sequence corresponding to the gene.

Survival motor neuron (SMN) gene: a gene for spinal muscular atrophy

Method and probes for detecting markers linked to the infantile spinal

Growing community of inventors

Paris, France

Arnold Munnich