# Advancing our Understanding of Rare Pediatric Liver Diseases

> **NIH NIH U01** · CHILDREN'S HOSP OF PHILADELPHIA · 2020 · $177,660

## Abstract

PROJECT SUMMARY
This proposal is in response to a request for applications for the Continuation of ChiLDReN, the Childhood
Liver Disease Research Network. Over the past fifteen years, through a coordinated effort, investigations of
eight cholestatic pediatric disorders have been advanced and we have established a robust database and
biorepository for further research. Little is known about the pathogenesis, natural history, and optimal
treatment strategies for the rare pediatric liver diseases investigated by ChiLDReN. We at The Children's
Hospital of Philadelphia (CHOP) propose to continue to participate in this Consortium, and thereby advance
the field through collaborative research. Only through collaboration can we improve the quality and efficiency
of care provided to all individuals diagnosed with one of the diseases studied by this network.
CHOP has been a highly productive member of ChiLDReN for the last 15 years. In this application, we
propose to continue our participation in all aspects of the ChiLDReN consortium, including clinical trials,
observational and interventional study protocols, genomics initiatives, dissemination of research findings and
ancillary studies. In addition, we have included a proposal for validation of candidate genes and proteins
identified through Network Genomics and Biomarker studies through two Aims. 1) We propose to develop
control and disease-specific tissue microarrays (TMA) for high throughput analysis of protein localization; 2)
We propose to investigate the function of candidate genes in a zebrafish model.
Alagille syndrome (ALGS) is an autosomal dominant disorder characterized by bile duct paucity and
cholestasis along with manifestations in other organ systems. Many ALGS patients have profound cholestasis,
with significantly elevated bilirubin and bile acids, development of xanthomas and severe pruritus that has a
major impact on quality of life. Despite the debilitating effects of pruritus on many aspects of daily life,
including school and sleep, there are few effective medical therapies. Patients who continue to experience
intractable pruritus despite treatment with all available therapies may require surgical intervention such as
biliary diversion, or even liver transplantation in the most refractory cases. Therefore, there is a critical unmet
need for safe and effective medical therapies for the cholestasis of pruritus in ALGS and other disorders. We
propose to conduct a randomized, double-blind crossover study of sertraline for the treatment of pruritus in
Alagille syndrome. Outcome measures will assess changes in pruritus, sleep, quality of life and autotaxin
activity after treatment with active drug or placebo. Safety and tolerability will also be assessed. Successful
completion of this study will determine the efficacy of sertraline as a therapy for pruritus in ALGS and
potentially identify sleep variables that could be used as objective study endpoints in this population. We
anticipate tha...

## Key facts

- **NIH application ID:** 10216063
- **Project number:** 3U01DK062481-19S1
- **Recipient organization:** CHILDREN'S HOSP OF PHILADELPHIA
- **Principal Investigator:** Kathleen Mary Loomes
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $177,660
- **Award type:** 3
- **Project period:** 2002-09-15 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10216063

## Citation

> US National Institutes of Health, RePORTER application 10216063, Advancing our Understanding of Rare Pediatric Liver Diseases (3U01DK062481-19S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10216063. Licensed CC0.

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