Molecular Pathogenesis and Epigenetic Rescue of Novel Human Models of ZC4H2-associated rare disorders.

Awardee: Julian Halmai

Institution: UC Davis

Grant Amount: $54,187

Funding Period: February 1, 2025 - January 31, 2026

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Summary:

The main objectives of this project are to establish human models of three unique loss of function ZARD variants within control sex-matched IMR90 NSC, using gene editing and to characterize the cellular and molecular phenotypes associated with ZARD pathology, with interest in understanding the link between ZC4H2 loss of function and BMP-Smad signaling pathway dysregulation. This proposal, if successful with shed light onto ZARD related pathology and the potential targets for therapeutic intervention.

Neuromuscular Activation of Muscle in Children with the ZC4H2 Mutation

Awardee: Richard Lieber

Institution: Shirley Ryan AbilityLab

Grant Amount: $61,815.00

Funding Period: February 1, 2024 - January 31, 2025

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Summary:

Our research will determine whether the weakness experienced by children with the ZC4H2 mutation is due to their inability to voluntarily recruit muscle groups or weakness in the muscle itself. This will be accomplished by measuring both mechanical and electrical activity of the major flexors and extensors in the body. In this way, we can focus development on therapies related to the actual functional problem in these children.

Targeted reactivation of ZC4H2 using miniature Cas editors

Awardee: Julian Halmai

Institution: University of California, Davis

Grant Amount: $46,846.00

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

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Summary:

The overall goal of this proposal is to develop CRISPR therapeutics for ZC4H2 Associated Rare Disorders. If successful, reactivation of the X-linked ZC4H2 could result in rescue of disease associated phenotypes in female patients affected by the disorder. This proposal utilizes AAV ready miniature epigenome editors that have great potential to improve the field of extant CRISPR therapeutics.

Structural and Functional Investigation of the ZC4H2 Protein

Awardee: Fahad Ali

Institution: Mohammed Bin Rashid University Of Medicine and Health Sciences

Grant Amount: $46,846.00

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

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Summary:

ZC4H2 Associated Rare Disorders (ZARD) is a rare genetic disorder that impacts the nervous system. It is caused by mutations within the ZC4H2 gene. ZC4H2 codes for a protein that, as of yet, has not been studied and is of unknown function. In this project, we aim to investigate this function using a combination of cellular and molecular approaches to guide future therapeutic development.