Biochemical investigation of NUBPL disease mechanisms and therapy candidates

Awardee: Eiko Ogiso

Institution: Children's Hospital of Philadelphia

Grant Amount: $120,465.00

Funding Period: February 1, 2023 - January 31, 2024

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Summary:

The goal of this project is to unveil NUBPL disease mechanisms and accelerate identification of therapeutic candidates that improves health in human NUBPL disease patients. Toward this goal, we utilize three NUBPL-/- genetic disease models, C. elegans (worm, invertebrate), D. rerio (zebrafish, vertebrate), and human patient cells. First, we will investigate therapeutic efficacy of top drug candidates recently identified in other complex I disease worms as well as nutrient and signaling pathway modulators (including vitamins and dietary supplements), in our NUBPL-/- zebrafish and human patient fibroblasts. Second, we will expand our focus on iron regulation and metabolism including response to iron therapy, which might also be involved in NUBPL disease pathogenesis outside complex I deficiency. Third, we will generate induced pluripotent stem cells (iPSCs) from NUBPL patient cells and differentiate neurons from iPSCs to develop a model to study neuronal-specific effects of NUBPL disease and validate efficacies of candidate therapies at neuronal levels.

Pre-clinical investigation of candidate therapies for NUBPL disease

Awardee: Neal Mathew

Institution: Children's Hospital of Philadelphia

Grant Amount: $50,198

Funding Period: February 1, 2022 - January 31, 2023

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Summary:

The overall goal of this project is to identify lead therapeutic candidates for NUBPL-/- based mitochondrial disease. We hypothesize that therapeutic modeling of NUBPL-/- genetic disease across 3 evolutionarily distinct models will enable identification and optimization of a lead therapeutic regimen to prioritize as a precision medicine that improves health in human NUBPL-/- disease patients.

Characterizing the Natural History of NUBPL-related Mitochondrial Disease

Awardee: Zarazuela Zolkipli-Cunningham

Institution: Children's Hospital of Philadelphia

Award Amount: $75,360

Funding Period: February 1, 2021 - January 31, 2022

Pre-clinical animal model and cell evaluation of candidate therapies for human NUBPL disease.

Awardee: Marni Falk

Institution: Children's Hospital of Philadelphia and University of Pennsylvania

Award Amount: $61,134