Cantú syndrome (CS) is a rare condition characterized by excess hair growth, a distinctive facial appearance, heart defects, and skeletal abnormalities. The goal of this proposed project is to understand the mechanisms of CS and develop appropriate treatments. The team has discovered gain-of-function (GOF) mutations in KATP channels as the genetic cause, initiated the world’s only CS registry and clinic, and developed unique transgenic animals for understanding mechanisms and treatments.
The aims of this proposal are to:
1. Determine the mechanisms of CS pathology: The team has developed animals carrying CS mutations and will utilize tissues derived from induced pluripotent stem cells to assess KATP GOF-induced abnormalities and explain disease features.
2. Develop a CS therapy: The team will further develop the world’s first CS registry and clinic and will test the efficacy of KATP-blocking sulfonylurea compounds, which are approved for use in type 2 diabetes. The efficacy will be tested in animal models and the safety in CS patients.
The proposed research will provide novel insights into the role of KATP channels in organ development and pathobiology, establish St. Louis Children’s Hospital and Washington University as the world center for CS, and ultimately bring novel treatment options for this debilitating syndrome and related diseases.
Dorothy Grange, M.D., Beth Kozel, M.D., Ph.D., Maria Remedi, Ph.D., Gautam Singh, M.D.