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BFU2010-21823

Financiado

MODELADO DE PATOLOGIAS NEURODEGENERATIVAS MEDIANTE CELULAS MADRE CON PLURIPOTENC...

MODELADO DE PATOLOGIAS NEURODEGENERATIVAS MEDIANTE CELULAS MADRE CON PLURIPOTENCIA INDUCIDA PARKINSON¿S DISEASE (PD) IS AMONG THE MOST FREQUENT HUMAN NEURODEGENERATIVE DISORDERS AND IS CAUSED BY THE LOSS OF MIDBRAIN DOPAMINERGIC NEURONS IN THE SUBSTANTIA NIGRA, NONE OF THE CURRENTLY APPROVED DRUGS SIGNIFICANTLY PREVENTS... ver más

01/01/2010

189K€

Presupuesto del proyecto: 189K€

Líder del proyecto

UNIVERSIDAD DE BARCELONA No se ha especificado una descripción o un objeto social para esta compañía.

Total investigadores 327

Financiación concedida El organismo AGENCIA ESTATAL DE INVESTIGACIÓN notifico la concesión del proyecto el día 2010-01-01 No tenemos la información de la convocatoria

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UNIVERSIDAD DE BARCELONA No se ha especificado una descripción o un objeto social para esta compañía.

Total investigadores 327

Presupuesto del proyecto 189K€

Descripción del proyecto PARKINSON¿S DISEASE (PD) IS AMONG THE MOST FREQUENT HUMAN NEURODEGENERATIVE DISORDERS AND IS CAUSED BY THE LOSS OF MIDBRAIN DOPAMINERGIC NEURONS IN THE SUBSTANTIA NIGRA, NONE OF THE CURRENTLY APPROVED DRUGS SIGNIFICANTLY PREVENTS PD PROGRESSION, THUS, IT IS URGENT TO ESTABLISH NEW THERAPIES THAT CAN BE COMBINED TO THE EXISTING TREATMENTS TO FURTHER IMPROVE PATIENT LIFE QUALITY AND POSSIBLY TO SLOW OR BLOCK DISEASE PROGRESSION, FOR THIS PURPOSE, IT IS CRITICAL TO GAIN A FULL UNDERSTANDING OF THE CELLULAR AND MOLECULAR MECHANISMS OF PD, HOWEVER, DESPITE A TREMENDOUS WEALTH OF NEW INFORMATION ABOUT THE MOLECULAR BASIS OF THE DISEASE, THE LACK OF FAITHFUL CELLULAR AND ANIMAL MODELS IS DELAYING THE DEVELOPMENT OF NEW THERAPEUTICS, THE RECENT GENERATION OF INDUCED PLURIPOTENT STEM CELL (IPSC) BY ECTOPIC EXPRESSION OF A DEFINED SET OF FACTORS ENABLES THE DERIVATION OF PATIENT-SPECIFIC PLURIPOTENT CELLS, THUS PROVIDING VALUABLE EXPERIMENTAL PLATFORMS TO MODEL HUMAN DISEASE, HERE, WE WILL COMBINE OUR EXPERTISE IN DIRECTED DIFFERENTIATION OF MIDBRAIN DOPAMINERGIC NEURONS AND ON INDUCED REPROGRAMMING TO DEVELOP AND TEST NOVEL, GENUINELY HUMAN EXPERIMENTAL MODELS OF PD, SPECIFICALLY, WE PROPOSE: 1) TO DEVELOP AN EFFICIENT PROTOCOL FOR THE DIFFERENTIATION OF HUMAN PLURIPOTENT STEM CELLS TO MIDBRAIN DOPAMINERGIC NEURONS, BUILDING ON PRELIMINARY RESULTS FROM OUR LABORATORY THAT SHOW THAT CONTROLLED OVER-EXPRESSION OF KEY TRANSCRIPTION FACTORS IS ABLE TO COAX NEURAL PROGENITORS INTO ADOPTING A VENTRAL MESENCEPHALIC DOPAMINERGIC PHENOTYPE; 2) TO CHARACTERIZE CONTROL VERSUS PD-SPECIFIC IPSC-DERIVED NEURONS WITH REGARDS TO MORPHOLOGY, AGGREGATES AND DOPAMINE RELEASE, USING LINES OF PATIENT-SPECIFIC IPSC REPRESENTING SPECIFIC GENETIC MUTATIONS AS WELL AS SPORADIC PD PATIENTS; AND 3) TO DEVELOP GENUINELY HUMAN CELL CULTURE MODELS OF PD BASED ON CO-CULTURES OF DOPAMINERGIC NEURONS AND ASTROCYTES, WHICH WILL BE DIFFERENTIATED FROM CONTROL AND/OR PD-SPECIFIC IPSC LINES, THE GENERATION OF ¿HUMANIZED¿ MODELS OF PD WILL NOT ONLY ALLOW THE VALIDATION OF OUR NEURONAL DIFFERENTIATION PROTOCOL IN THE COMPLEX CONTEXT OF PD, BUT ALSO PROVIDE A GENUINELY HUMAN EXPERIMENTAL MODEL OF PD THAT WILL BE PREDICTIVE OF THE THERAPEUTIC RESPONSE IN HUMANS, THE SUCCESSFUL ACHIEVEMENTS OF OUR GOALS WILL DISCLOSE NEW OPPORTUNITIES FOR DISEASE MODELING AND DRUG SCREENING IN PD,

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