Description du projet
Les facteurs sanguins de rajeunissement et de vieillissement comme cibles thérapeutiques de la maladie d’Alzheimer
Le vieillissement est le facteur de risque le plus important de la maladie d’Alzheimer (MA). Le projet HeBe, financé par l’UE, vise à découvrir des facteurs sanguins ayant un effet de rajeunissement ou de vieillissement sur le cerveau humain afin de développer des cibles thérapeutiques pour la MA. L’hypothèse est que des niveaux plus élevés de facteurs sanguins rajeunissants diminuent le taux de neurodégénérescence, alors que des niveaux plus élevés de facteurs sanguins vieillissants l’augmentent. L’étude définira des phénotypes d’âge biologique extrême chez les femmes et les hommes en fonction de la différence entre l’âge biologique et l’âge chronologique. Elle emploiera la protéomique et la métabolomique pour identifier les facteurs sanguins qui diffèrent entre ces phénotypes extrêmes et développera des tests pour mesurer ces facteurs dans des cohortes longitudinales de personnes qui ne présentent aucune déficience cognitive et de personnes atteintes de la MA préclinique.
Objectif
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.
Champ scientifique
Programme(s)
Thème(s)
Régime de financement
ERC-STG - Starting GrantInstitution d’accueil
08005 Barcelona
Espagne