Nicolas Ferry

Bio: Nicolas Ferry is an academic researcher from French Institute of Health and Medical Research. The author has contributed to research in topics: Transgene & Genetic enhancement. The author has an hindex of 26, co-authored 75 publications receiving 2176 citations. Previous affiliations of Nicolas Ferry include École Normale Supérieure & Pasteur Institute.

Gene therapy of the brain in the dog model of Hurler's syndrome.

Abstract: Objective A defect of the lysosomal enzyme α-L-iduronidase (IDUA) interrupts the degradation of glycosaminoglycans in mucopolysaccharidosis type I, causing severe neurological manifestations in children with Hurler's syndrome. Delivery of the missing enzyme through stereotactic injection of adeno-associated virus vectors coding for IDUA prevents neuropathology in affected mice. We examined the efficacy and the safety of this approach in enzyme-deficient dogs. Methods Because deficient dogs raise antibodies against IDUA in response to infusion, intracerebral vector injections were combined with an immunosuppressive regimen. Results Treatment was tolerated well. We observed broad dispersion of vector genomes in the brain of efficiently immunosuppressed dogs. The delivery of IDUA to large areas, which could encompass the entire brain, prevented glycosaminoglycan and secondary ganglioside accumulations. This condition was associated with drastic reduction of neuropathology throughout the encephalon. In contrast, vector injection combined with partial immunosuppression was associated with subacute encephalitis, production of antibodies against IDUA in brain tissues, and elimination of genetically modified cells. Interpretation Gene therapy directed to the entire brain is feasible and may be beneficial to children with Hurler's syndrome. The possibility of subacute encephalitis emphasizes the importance of preventing immune response against IDUA, a problem that needs to be considered in similar therapies for other genetic defects. Ann Neurol 2006;

Inositol trisphosphate, a novel second messenger in cellular signal transduction.

Abstract: There has recently been rapid progress in understanding receptors that generate intracellular signals from inositol lipids. One of these lipids, phosphatidylinositol 4,5-bisphosphate, is hydrolysed to diacylglycerol and inositol trisphosphate as part of a signal transduction mechanism for controlling a variety of cellular processes including secretion, metabolism, phototransduction and cell proliferation. Diacylglycerol operates within the plane of the membrane to activate protein kinase C, whereas inositol trisphosphate is released into the cytoplasm to function as a second messenger for mobilizing intracellular calcium.