Predictive approaches to mitigate risk of hepatotoxicity of drugs in children
NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development
About This Grant
ABSTRACT Understanding and mitigating drug-induced liver injury (DILI) in children is crucial for pediatric healthcare. Children are more prone to liver damage due to differences in drug metabolism, liver development, and unique susceptibilities. DILI can cause immediate health risks and long-term issues like liver failure or chronic liver disease. Since children often need medications for chronic diseases such as epilepsy, infections, and pain, ensuring the safety of drugs is vital. Addressing DILI in children through advanced methods not only improves drug safety but also supports personalized medicine, enhancing care quality and reducing adverse drug reactions. For example, acetaminophen, commonly used for pain and fever, can cause severe liver damage. Valproic acid, used for epilepsy, also poses a risk of liver toxicity, especially with long-term use. In this proposal, we would like to investigate mechanisms of toxicity of acetaminophen, valproic acid, amoxicillin- clavulanate, cannabidiol (CBD), and isoniazid, which covers critical pharmaceuticals in pediatric healthcare, and develop biomarkers of pediatric DILI caused by these pharmaceuticals. The proposal has two main aims. Aim 1 is to evaluate the effect of selected drugs on liver toxicity markers using a sandwich cultured human hepatocyte model leveraging primary human hepatocytes from pediatric and adult donors. This will involve measuring proteomic and metabolomic biomarkers in drug-treated hepatocyte lots from infants, children, adolescents, and adults to understand age-specific mechanisms of DILI. The study will also analyze proteomics data of extracellular vesicles and untargeted metabolomics of media to identify molecular changes and drug-protein adducts. These data will be integrated into mathematical models using quantitative systems toxicology (QST) models to predict pathways and mechanisms of DILI. Aim 2 will measure the effects of acute and prolonged drug exposure using liver microphysiological system (MPS) using standardized liver tissue chip. By analyzing proteins and metabolites released in the media from these systems, the study will assess immediate and long-term impacts on liver function and toxicity in both pediatric and adult livers. Overall, utilizing advanced methodologies such as proteomics, metabolomics, and complex in vitro models, including MPS, the research will assess DILI across various pediatric age groups. Integrating these findings into mathematical models will provide a deeper understanding of DILI mechanisms and potentially identify specific biomarkers relevant to children. Ultimately, when validated in clinic, pediatric DILI candidate biomarkers will enhance drug safety profiles, inform better prescribing practices, and support personalized treatment approaches in children.
Grant Summary
Predictive approaches to mitigate risk of hepatotoxicity of drugs in children is a NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development grant providing up to $446K for university, nonprofit, healthcare org. Applications are due 2027-08-31 (open). Check eligibility and apply with FindGrants.
Not quite the right fit?
Search 9,000+ open grants, or get matches ranked for your organization — free.
Focus Areas
Eligibility
How to Apply
Up to $446K
2027-08-31
- 1Confirm your organization is eligible for Predictive approaches to mitigate risk of hepatotoxicity of drugs in children from NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development, checking organization type, location, and any population or project requirements.
- 2Gather the required documents and information, including your organization details, project plan, and budget figures.
- 3Draft your application narrative and budget addressing the funder's priorities and review criteria. FindGrants can draft each section for you to review and edit.
- 4Review every section against the requirements checklist, then export a submission-ready application pack and submit it to NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development before the deadline.
Don't want to draft it yourself?
We'll draft the complete application against NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development's requirements, run a quality review, and email you a submission-ready PDF plus an editable Word doc within 5 business days. Most orders deliver in 24-48 hours. Flat $399, any grant size.
AI Requirement Analysis
Detailed requirements not yet analyzed
Have the NOFO? Paste it below for AI-powered requirement analysis.
Predictive approaches to mitigate risk of hepatotoxicity of drugs in children: Frequently Asked Questions
Who is eligible for the Predictive approaches to mitigate risk of hepatotoxicity of drugs in children?
Predictive approaches to mitigate risk of hepatotoxicity of drugs in children is offered by NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
How much funding does the Predictive approaches to mitigate risk of hepatotoxicity of drugs in children provide?
Predictive approaches to mitigate risk of hepatotoxicity of drugs in children provides up to $446K per award from NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the Predictive approaches to mitigate risk of hepatotoxicity of drugs in children deadline?
Applications for Predictive approaches to mitigate risk of hepatotoxicity of drugs in children are due 2027-08-31 (open). Because deadlines can change, verify the date with the funder, NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the Predictive approaches to mitigate risk of hepatotoxicity of drugs in children?
To apply for Predictive approaches to mitigate risk of hepatotoxicity of drugs in children, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development.