Antikroppsbaserad PET vid neurodegenerativa sjukdomar

Tidsperiod: 2018-01-01 till 2021-12-31

Finansiär: Vetenskapsrådet

Bidragstyp: Projektbidrag

Budget: 4 800 000 SEK

Aim: To develop antibody (mAb) based Positron Emission Tomography (PET) ligands for use in Alzheimer’s (AD) and Parkinson’s disease (PD) with dynamic and specific properties correlating with disease severity.Current status: All available amyloid PET-ligands used for AD diagnosis bind to amyloid-beta (Aß) plaques although earlier formed soluble Aß aggregates seem to correlate better with disease severity. All efforts to develop small molecular PET-ligands for alpha-synuclein (α-syn), the pathogenic protein in PD, have so far been unsuccessful. Work plan: PET ligands will be generated based on bispecific mAbs displaying affinity for two targets simultaneously: 1) aggregates, including soluble forms, of Aß or α-syn and 2) receptors at the blood-brain barrier that can be used as Trojan horses to actively deliver the bispecific mAbs into the brain.  In 2016 we showed this concept to be successful in mice, with the first mAb based PET-ligand for a brain target. We will now develop this technology for clinical use and for applications in other neurodegenerative diseases. The project will be performed at Dep Public Health/Caring Sciences, UU in close collaboration with the PET facilities at UU and the Academic Hospital. Expected results: Besides advancing mAb based PET for the brain, the new ligands will be used to follow and predict disease progression and to evaluate effects of emerging treatments, i.e. two needs that are not satisfactory met today.