Descrizione del progetto
Scansione PET per la diagnosi di schizofrenia
La diagnosi di schizofrenia rappresenta una sfida medica significativa a causa dell’assenza di biomarcatori specifici. Sebbene l’evidenza suggerisca un’espressione differenziale dei recettori dell’acido gamma-aminobutirrico (GABA) nel cervello dei pazienti con questo disturbo mentale, ciò deriva dagli studi post mortem. Pertanto, gli scienziati del progetto GABARPET, finanziato dall’UE, propongono di sviluppare sonde per tomografia a emissione di positroni (PET) in grado di svelare informazioni quantitative sull’espressione specifica di subunità di recettori GABAA nei pazienti. Per superare l’impermeabilità della barriera emato-encefalica, queste sonde PET saranno create come anticorpi bi-specifici che hanno come target sia il GABAA che i recettori della transferrina. I risultati forniranno una visione fondamentale della biologia della schizofrenia e miglioreranno la diagnosi della malattia.
Obiettivo
Changes in GABA receptors are known hallmarks for numerous neurological diseases including schizophrenia which is a severe psychiatric disorder that has a profound effect on both the individuals affected and society. The diagnosis of schizophrenia is complex because of the loss of high specific biomarkers. Research papers have suggested that the differential expression of GABAA receptors in the brain is associated with this mental disease. The current evidence on GABAergic abnormalities in schizophrenia is mostly based on postmortem studies and, in this sense, in vivo measurements of GABAA receptor subunits can reveal additional insights.
This project will develop Positron Emission Tomography (PET) probes which could unveil quantitative information about GABAA receptor expression in schizophrenia patients. However, the lack of imaging tracers with high affinity and specificity do not shed a clear light on the diagnosis in a traditional PET setting. In this sense, the immune-positron emission tomography (immunoPET) is a non-invasive technology based in antibody imaging which reveals a specific and sensitive molecular characterization of the cell surface phenotype in vivo. Nevertheless, its success in neuroimage is limited because of intact antibodies cannot penetrate the Brain Blood Barrier (BBB) in healthy conditions. However, GABARPET will tap into a small recombinant bispecific antibody construct targeting the GABAA receptors as well as the transferrin receptor because it is able to readily transmigrate across the BBB in vivo after peripheral injection.
This project wants to develop di-single-chain variable fragment (di-scFv) directed to α1 and α2 subunits of GABAA receptors. Then, they will be labeled with conventional radionuclides produced by cyclotron as 18F and 89Zr. ImmunoPET probes will be used in wild-type mice, GABAA receptor knockout mice and different kind of rodent models of schizophrenia.
Campo scientifico
Parole chiave
Programma(i)
Argomento(i)
Meccanismo di finanziamento
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinatore
20014 Turku
Finlandia