Transplanted organoids empower human preclinical assessment of drug candidate for the clinic.

Autor:	Westerling-Bui AD; Goldfinch Bio Inc., Cambridge, MA 02142, USA., Fast EM; Goldfinch Bio Inc., Cambridge, MA 02142, USA., Soare TW; Goldfinch Bio Inc., Cambridge, MA 02142, USA., Venkatachalan S; Goldfinch Bio Inc., Cambridge, MA 02142, USA., DeRan M; Diamond Age Data Science, Somerville, MA 02143, USA., Fanelli AB; Goldfinch Bio Inc., Cambridge, MA 02142, USA., Kyrychenko S; Goldfinch Bio Inc., Cambridge, MA 02142, USA., Hoang H; Goldfinch Bio Inc., Cambridge, MA 02142, USA., Corriea GM; Goldfinch Bio Inc., Cambridge, MA 02142, USA., Zhang W; Goldfinch Bio Inc., Cambridge, MA 02142, USA., Yu M; Goldfinch Bio Inc., Cambridge, MA 02142, USA., Daniels M; Goldfinch Bio Inc., Cambridge, MA 02142, USA., Malojcic G; Goldfinch Bio Inc., Cambridge, MA 02142, USA., Pan-Zhou XR; Goldfinch Bio Inc., Cambridge, MA 02142, USA., Ledeboer MW; Goldfinch Bio Inc., Cambridge, MA 02142, USA., Harmange JC; Goldfinch Bio Inc., Cambridge, MA 02142, USA., Emani M; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA., Tibbitts TT; Goldfinch Bio Inc., Cambridge, MA 02142, USA., Reilly JF; Goldfinch Bio Inc., Cambridge, MA 02142, USA., Mundel P; Goldfinch Bio Inc., Cambridge, MA 02142, USA.
Jazyk:	angličtina
Zdroj:	Science advances [Sci Adv] 2022 Jul 08; Vol. 8 (27), pp. eabj5633. Date of Electronic Publication: 2022 Jul 06.
DOI:	10.1126/sciadv.abj5633
Abstrakt:	Pharmacodynamic (PD) studies are an essential component of preclinical drug discovery. Current approaches for PD studies, including the analysis of novel kidney disease targeting therapeutic agents, are limited to animal models with unclear translatability to the human condition. To address this challenge, we developed a novel approach for PD studies using transplanted, perfused human kidney organoids. We performed pharmacokinetic (PK) studies with GFB-887, an investigational new drug now in phase 2 trials. Orally dosed GFB-887 to athymic rats that had undergone organoid transplantation resulted in measurable drug exposure in transplanted organoids. We established the efficacy of orally dosed GFB-887 in PD studies, where quantitative analysis showed significant protection of kidney filter cells in human organoids and endogenous rat host kidneys. This widely applicable approach demonstrates feasibility of using transplanted human organoids in preclinical PD studies with an investigational new drug, empowering organoids to revolutionize drug discovery.
Databáze:	MEDLINE
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