Understanding the pathophysiology of Keutel Syndrome: A path towards cure

• Applicant: Professorin Dr. Magali Cucchiarini, Ph.D.
• Subject Area: Pathology ; Orthopaedics, Traumatology, Reconstructive Surgery
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 441083034

Keutel Syndrome (KS) is a rare genetic disease caused by mutations in MGP gene. The major KS traits include inborn facial disfigurements, cross-bites and serious respiratory complications, which may lead to premature deaths. Our studies on MGP-deficient mice, a faithful model of KS, show that pathologic mineral deposition (ectopic calcification) in cartilaginous tissues is the primary cause underlying these abnormalities. At present only symptomatic treatments are available, which often fail to prevent the progression of KS pathology. Our lack of understanding of how MGP prevents pathologic calcification of various cartilages is still missing. This lack of information is seriously hampering the process of novel drug development and treatment strategies for KS patients. We will use cutting-edge genetics and analytical techniques to address this gap of knowledge.This mechanistic study using genetically modified mouse and zebrafish models will identify the relevant functional domains in MGP required for the prevention of abnormal cartilage calcification and provide information about the nature of the critical sites of mineral accumulation associated with the major KS traits. Understanding the mechanism of action of MGP as a mineralization inhibitor will have important implications for the treatment of KS patients in future.

• DFG Programme: Research Grants
• International Connection: Canada, France, Portugal
• Cooperation Partners: Professorin Dr. Leonor Cancela; Privatdozent Dr. Herve Kempf, Ph.D.; Professor Dr. Monzur Murshed