Descripción del proyecto
Factores hematológicos del envejecimiento y el rejuvenecimiento como dianas terapéuticas de la enfermedad de Alzheimer
El envejecimiento es el factor de riesgo más importante de la enfermedad de Alzheimer (EA). El proyecto HeBe, financiado con fondos europeos, pretende descubrir factores hematológicos con un efecto envejecedor o rejuvenecedor sobre el encéfalo humano para desarrollar dianas terapéuticas para la EA. La hipótesis es que unos niveles más elevados de factores hematológicos del rejuvenecimiento disminuyen el índice de neurodegeneración, mientras que unos niveles más elevados de factores hematológicos del envejecimiento lo aumentan. El estudio definirá fenotipos de edad biológica extrema en mujeres y hombres en función de la diferencia entre la edad biológica y la cronológica. Utilizará la proteómica y la metabolómica para identificar los factores hematológicos que difieren entre estos fenotipos extremos y desarrollar ensayos para medir estos factores en cohortes longitudinales de individuos con EA preclínicos y cognitivamente intactos.
Objetivo
One of the most exciting findings in neuroscience has been the discovery of peripheral blood factors with rejuvenating or ageing effects on the mouse brain. These factors were discovered by parabiosis experiments in which the blood circulation of young and old animals is fused. The findings imply that the properties of young blood can rejuvenate the older brain. Ageing is the most important risk factor for Alzheimer’s Disease (AD), but there have been only limited attempts to develop therapies targeting the ageing process. Also, it is not known whether humans have similar blood factors that could be therapeutic targets in AD.
The overall aim of the HeBe project is to discover blood factors with a rejuvenating or ageing effect on the human brain that can thus become therapeutic targets for AD and other age-related brain diseases. For ethical reasons, parabiosis experiments are not possible in humans. HeBe will circumvent this problem using a highly original approach in which I will define extreme biological age phenotypes in women and men based on the difference between biological and chronological age. I will use advanced proteomics and metabolomics to identify blood factors that differ between these extreme phenotypes, and then develop a targeted assay toolkit to measure these factors in large longitudinal cohorts of cognitively unimpaired and preclinical AD individuals.
The main hypothesis of HeBe is that higher levels of rejuvenating blood factors decrease the rate of neurodegeneration, while higher levels of ageing blood factors increase the rate of neurodegeneration. If this hypothesis is confirmed, I will provide a new therapeutic target for AD. By the end of HeBe, I will also design a proof-of-concept clinical trial to assess whether life-style or pharmacological interventions modify blood levels of rejuvenating or ageing factors. Thus, the HeBe project is the first and a key step in the translational continuum towards interventions in clinical practice.
Ámbito científico
Not validated
Not validated
Programa(s)
Régimen de financiación
ERC-STG - Starting GrantInstitución de acogida
08005 Barcelona
España