To date, the Foundation has funded and/or supported the following ongoing research projects:

Neuromuscular Activation of Muscle in Children with the ZC4H2 Mutation

Dr. Richard Lieber, PhD- Shirley Ryan AbilityLab Chicago, Illinois, USA.

This research will determine whether the weakness experienced by children with ZC4H2 mutation is due to their inability to voluntarily recruit muscle groups or weaknesses 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.

Natural History Study on ZC4H2 Associated Rare Disorders (ZARD)

Dr. David Bearden, MD- University of Rochester, New York, USA.

This project, generously funded by the University of Rochester, is the first Natural History Study on ZC4H2 and aims to understand the natural progression of ZARD over time. With this study, we will be able to better understand ZARD and its prognosis and hopefully develop better treatments for children living with ZARD. The study will be conducted remotely and will have participants from all over the world. To enroll or find out more click here. 

Targeted reactivation of ZC4H2 using miniature Cas editors

Dr. Julian Halmai, PhD- University of California, Davis, USA.

Structural and Functional Investigation of the ZC4H2 Protein

Dr. Fahad Ali, PhD- Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, UAE.

Studies on ZC4H2 to help better understand the pathophysiology of ZARD

Dr. Vera Kalscheuer, PhD – Max Planck Institute for Molecular Genetics, Berlin, Germany.

This project focuses on the creation of an antibody to detect the ZC4H2 protein. This will be beneficial to all researchers studying the disease.Funds will also go to creating mouse models with the same mutations as ZC4H2 patients. RNAseq analysis is performed on embryos from the mouse models, which is a technique to look at expression of all proteins in the cell. This may reveal pathways affected by loss of the protein during early development.

Nucleic acid binding by ZC4H2

Prof. Daniel Dominguez, PhD – University of North Carolina at Chapel Hill, USA.

ZC4H2 was identified as a protein that binds to DNA. This project focuses on the identification of different target DNA sequences that the protein binds to. The results may reveal proteins in pathways that require ZCH42 for appropriate function.

Deciphering the structural consequences of ZC4H2 germline rare variants

Prof. Michal Linial – The Hebrew University of Jerusalem, Israel.

In this research project, computational modeling is used to study ZC4H2 protein-protein interactions. The research looks at interactions of ZC4H2 with its known binding partner SMAD, a protein involved in neuronal development. This research may reveal why specific mutations in ZC4H2 affect binding to its target proteins.

Creation of an Induced Pluripotent Stem Cell (iPSC) line

The Coriell Institute for Medical Research.Camden, NY. USA, 2022.

This project aims to develop the first iPSC line from a ZARD patient. The cells will be stored and available for usage in any future research projects.

Analysis of the morphology and biology of skeletal muscles in ZARD

Prof. R. Lieber and Dr. Rajeswari Pichika – The Shirley Ryan AbilityLab & Northwestern University. Chicago, USA, 2022.

This first-ever study on the morphology and biology of ZARD muscles is being conducted with biopsies from three different skeletal muscles of a female ZARD patient.