EIN2020-112367
Financiado
IDENTIFICACION DE NUEVAS DIANAS TERAPEUTICAS EN DEMENCIA
LA DEMENCIA ENGLOBA UN CONJUNTO DE ENFERMEDADES NEURODEGENERATIVAS CARACTERIZADAS POR UN DETERIORO PROGRESIVO DE LAS HABILIDADES COGNITIVAS DE UNA PERSONA, INHABILITANDO LA REALIZACION DE LAS ACTIVIDADES DIARIAS DE MANERA INDEPEND...
LA DEMENCIA ENGLOBA UN CONJUNTO DE ENFERMEDADES NEURODEGENERATIVAS CARACTERIZADAS POR UN DETERIORO PROGRESIVO DE LAS HABILIDADES COGNITIVAS DE UNA PERSONA, INHABILITANDO LA REALIZACION DE LAS ACTIVIDADES DIARIAS DE MANERA INDEPENDIENTE, COMO ES EL CASO DE LA ENFERMEDAD DE ALZHEIMER (EA), LA DEMENCIA FRONTOTEMPORAL (FTD) O LA DEMENCIA DE LOS CUERPOS DE LEWY (DLB). DEMENTIA IS A SYNDROME ENGLOBING DIFFERENT NEURODEGENERATIVE DISORDERS CHARACTERIZED BY A PROGRESSIVE IMPAIRMENT OF COGNITIVE FUNCTIONS, ULTIMATELY HAMPERING THE PERFORMANCE OF DAILY LIFE ACTIVITIES. THEY ARE AGE-RELATED NEURODEGENERATIVE DISORDERS AND AS LIFE SPAN INCREASES, DEMENTIA WILL POSE A HUGE IMPACT NOT ONLY ON THE PATIENTS AND THEIR FAMILIES, BUT ALSO ON THE PUBLIC HEALTHCARE SYSTEMS. 46 MILLIONS OF PEOPLE ARE SUFFERING FROM AD WORLDWIDE (1.9% SPANISH POPULATION), WITH ONE NEW CASE DIAGNOSED EVERY 3 SECONDS. IF NO CURE IS FOUND BEFORE 2050, IT IS EXPECTED THAT THE NUMBER OF PATIENTS SUFFERING OF DEMENTIA WILL BE TRIPLICATED, CHALLENGING THE ECONOMIC AND SOCIAL BURDEN WORLDWIDE. UNFORTUNATELY, THE CLINICAL TRIALS PERFORMED SO FAR HAVE BEEN DISAPPOINTING, WHICH IS PARTIALLY ATTRIBUTED TO THE LIMITED KNOWLEDGE ABOUT THE UNDERLYING ETIOLOGICAL FACTORS. THUS, THERE IS AN URGENT NEED TO IDENTIFY NOVEL MECHANISMS UNDERLYING THE PATHOGENESIS OF DEMENTIA, WHICH WILL LIKELY PROMOTE THE DEVELOPMENT OF NOVEL ALTERNATIVE THERAPEUTIC STRATEGIES. THE IDENTIFICATION OF TARGETS FOR DRUG DEVELOPMENT AGAINST THE MOST FREQUENT, COMPLEX AND BURDENSOME DISEASES INCLUDING AD HAS BECOME ONE OF THE CORE AREAS OF RESEARCH. AN INNOVATIVE STRATEGY THAT IN THE LAST YEARS HAS REVEALED NOVEL POTENTIAL THERAPEUTIC TARGETS FOR DIFFERENT DISORDERS IS THE ANALYSIS OF PROTEIN QUANTITATIVE TRAIT LOCI (PQTLS), WHICH IDENTIFIES WHICH PROTEINS ARE ULTIMATELY AFFECTED BY THE DIFFERENT GENETIC VARIANTS (E.G. RISK FACTORS) AND THUS, IT REVEALS THE INTERMEDIATE MOLECULAR PATHWAYS THAT CONNECT GENOMIC VARIANCE TO DISEASE ENDPOINTS. IN THE FIELD OF AD, SEVERAL GENETIC RISK LOCI HAVE BEEN IDENTIFIED. UNFORTUNATELY, DESPITE THE ENORMOUS SCIENTIFIC ADVANCES AND EFFORTS EMPLOYED IN THE LAST DECADES, WE STILL DO NOT COMPLETELY UNDERSTAND THE EXACT MECHANISM(S) BY WHICH THE DIFFERENT GENETIC RISK VARIANTS INFLUENCE THE DEVELOPMENT OF THE DIFFERENT DEMENTIA TYPES. THIS IS OF PARAMOUNT IMPORTANCE, SINCE UNRAVELING THE CAUSAL MECHANISMS AND PROTEINS THAT ARE AFFECTED BY THE MAJOR DEMENTIA RISK FACTOR COULD PROVIDE NOVEL TARGETS AND THERAPEUTIC STRATEGIES TO COUNTER THE DEVELOPMENT OF AD AND RELATED DEMENTIAS. BY PERFORMING PQTLS ANALYSIS IN A LIMITED AMOUNT OF CASES (563), OUR TEAM HAS RECENTLY IDENTIFIED THAT THE LEVELS OF FIVE PROTEINS IN THE CEREBROSPINAL FLUID ARE INFLUENCED BY DIFFERENT DEMENTIAS GENETIC RISK FACTORS (CR1, ZCWPW1, APOE, GBA). SUCH PROTEINS REFLECT A DYSFUNCTION OF MECHANISMS KNOWN TO PLAY AN IMPORTANT ROLE IN THE DEVELOPMENT OF DEMENTIAS SUCH NEUROINFLAMMATION OR PROTEOSTASIS PATHWAYS. THEREFORE, OUR NOVEL PREVIOUS DATA PROVIDES NEW BIOLOGICAL CONNECTIONS BETWEEN THE MAIN DEMENTIA GENETIC RISK VARIANTS AND ITS UNDERLYING MECHANISMS OPENING NEW INSIGHTS INTO THE PATHOGENESIS OF DIFFERENT DEMENTIA TYPES. NOVTAD WILL AIM TO COMPLETE OUR PREVIOUS FINDINGS ANALYSING A HIGHER NUMBER OF PATIENTS AND PROTEINS, NOT ONLY TO REPLICATE OUR PRELIMINARY FINDINGS BUT ALSO TO GAIN POWER AND IDENTIFY NEW BIOLOGICAL CONNECTIONS. MOREOVER, WE WILL ADDITIONALLY ANALYSED THE RELEVANCE OF SUCH ASSOCIATIONS IN THE DEVELOPM EMENCIA\PQTL\GENOMICA\PROTEOMICA\FACTORES ETIOLOGICOS
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Línea de financiación: concedida
El organismo AGENCIA ESTATAL DE INVESTIGACIÓN notifico la concesión del proyecto el día 2020-01-01
Presupuesto
El presupuesto total del proyecto asciende a
10K€
Líder del proyecto
FUNDACION UNIVERSITARIA SAN PABLO CEU
No se ha especificado una descripción o un objeto social para esta compañía.
Total investigadores
20
Total investigadores
20