Pediatric cholestatic diseases studied and treated via genetic mouse models

Pediatric cholestatic diseases: Genetic models (PedChoGeM)

The project aims to develop humanised mouse models for pediatric cholestatic diseases which will facilitate the development and testing of novel therapeutic strategies. Albireo is a pharmaceutical company with proven expertise in the development of novel therapies for rare cholestatic liver diseases.

Innovation is needed because presently many children are suffering from cholestatic itch and end-stage liver disease, for which frequently no other therapy exists than liver transplantation. The development of novel therapeutic strategies has been hampered by the rare nature of these diseases (1:50,000-100,000 children), which precludes large scale investigations in humans. Only in 2021 the first drugs for pediatric cholestatic liver diseases (PFIC, Alagille syndrome) have received FDA and/or EMA approval.

The progress in science now allows to mimick rare pediatric cholestatic diseases in genetically “humanised” mouse models, with a human tyoe of bile composition and with the human pathological mutations incorporated. The development and testing of these new models will allow to exploire and test novel targets and therapeutic strategies, which will increase the chances the preclinical success will ultimately translate into clinical therapeutic efficacy in patients.

The project is expected to increase insights which genetic pediatric choelstatic liver diseases are amenable to medical interruption of the enterohepatic circulation by mean of inhibition of intestinal bile acid uptake (IBAT-inhibition).

Summary
Many pediatric cholestatic diseases are genetic in origin. Treatment has been largely symptomatic, leading to the need for liver transplantation in childhood in the majority of cases. Testing novel therapeutic strategies has been hampered by the rare nature of these diseases (1:50,000-100,000 children). This project aims to develop humanised PFIC animal models which will facilitate the development and testing of novel therapeutic strategies and will also be crucial to understand the mechanisms of (non-)responsiveness to specific interventions.
Technology Readiness Level (TRL)
1 - 1
Time period
48 months
Partners
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