The Orphan Disease Center at the University of Pennsylvania, in partnership with the ZC4H2 Deficiency Research Foundation, is pleased to announce the ZC4H2-Associated Rare Disorders (ZARD) Pilot Grant Program, offering up to three one-year awards at $50,000, each.  This funding opportunity is open to the international community.

Overview: 

Pathogenic mutations in the zinc finger C4H2-type gene (ZC4H2) are associated with a neurodevelopmental and neuromuscular disorder often diagnosed as a form of arthrogryposis multiplex congenita.  ZC4H2 is a protein-coding gene located on the X-chromosome and the mechanism by which ZC4H2 mutations lead to disease remain unclear. Due to the key clinical features of both males and females with these mutations, there is a growing recognition of this condition as a unique disorder that should be clinically recognized as ZARD. Recent research has found that due to variation in X-inactivation or the presence of significant mutations in ZC4H2 (such as full deletions), females may also present with a form of the disease, albeit less severe than male ZC4H2 patients. It is believed that the pathogenic variants of ZC4H2 may result in impairment of the central and peripheral nervous system through the impairment of neurologic development. 

They are seeking grant applications that progress the understanding of ZC4H2 basic biology or development of treatments and/or a cure for ZARD. While the RFA is broad in scope, priority will be given to grants that cover the following areas:

1. Unbiased approaches to discovering the protein function of ZC4H2, including, but not limited to, rescue, modifier or synthetic lethal screens in genetically tractable model organisms 
2. Molecular characterization of ZC4H2 and the effect of mutations on molecular and protein function using in vitro and in in vivo models (mouse and human where possible): 

   -identification and characterization of naturally occurring transcripts, including splice isoforms 

   -spatio-temporal expression patterns of wildtype ZC4H2 expression at RNA and protein level (i.e. developmental time course and tissue- and cell type-specific expression of RNA and protein; cellular sub-localization of protein)  

3. Discovery and validation of druggable targets or pathways for ZC4H2 treatment. Pilot data should be already established. This grant would focus on validating the approach in a translatable experiment with clear Go/ No Go experiments. 

Letter of Interest Instructions:

Visit the Center’s website to submit your Letter of Interest (LOI). This one-page LOI is due no later than Monday, November 4, by 8 p.m.