ProMiDis
Financiado
A unified drug discovery platform for protein misfolding diseases
It is now widely recognized that a variety of major diseases, such as Alzheimer’s disease, Huntington’s disease, systemic amyloidosis, cystic fibrosis, type 2 diabetes etc., are characterized by a common molecular origin: the misf...
It is now widely recognized that a variety of major diseases, such as Alzheimer’s disease, Huntington’s disease, systemic amyloidosis, cystic fibrosis, type 2 diabetes etc., are characterized by a common molecular origin: the misfolding of specific proteins. These disorders have been termed protein misfolding diseases (PMDs) and the vast majority of them remain incurable. Here, I propose the development of a unified approach for the discovery of potential therapeutics against PMDs. I will generate engineered bacterial cells that function as a broadly applicable discovery platform for compounds that rescue the misfolding of PMD-associated proteins (MisPs). These compounds will be selected from libraries of drug-like molecules biosynthesized in engineered bacteria using a technology that allows the facile production of billions of different test molecules. These libraries will then be screened in the same bacterial cells that produce them and the rare molecules that rescue MisP misfolding effectively will be selected using an ultrahigh-throughput genetic screen. The effect of the selected compounds on MisP folding will then be evaluated by biochemical and biophysical methods, while their ability to inhibit MisP-induced pathogenicity will be tested in appropriate mammalian cell assays and in established animal models of the associated PMD. The molecules that rescue the misfolding of the target MisPs and antagonize their associated pathogenicity both in vitro and in vivo, will become drug candidates against the corresponding diseases. This procedure will be applied for different MisPs to identify potential therapeutics for four major PMDs: Huntington’s disease, cardiotoxic light chain amyloidosis, dialysis-related amyloidosis and retinitis pigmentosa. Successful realization of ProMiDis will provide invaluable therapeutic leads against major diseases and a unified framework for anti-PMD drug discovery.
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Duración del proyecto: 88 meses
Fecha Inicio: 2019-02-01
Fecha Fin: 2026-06-30
Fecha Fin: 2026-06-30
Línea de financiación: concedida
El organismo H2020 notifico la concesión del proyecto el día 2019-02-01
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
ERC-2018-COG:
ERC Consolidator Grant
Cerrada
hace 6 años
Presupuesto
El presupuesto total del proyecto asciende a
2M€
Líder del proyecto
EREVNITIKO KENTRO VIOIATRIKON EPISTIMON ALEXA...
No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico
TRL
4-5
Perfil tecnológico
TRL
4-5
2.07M€ |
Participante