How do we Treat Aberrant Excessive Signaling in FGF3 Receptor Pathway to Cure Achondroplasia in Childhood?

Abstract

In 1878, a French physician named Joseph Marie Jules Parrot coined the term achondrodysplasia. This term is purely historical and does not explain the cause or symptoms of the disorder. Other names that were once used but are now obsolete include chondrodystrophy, chondrodystrophia fetalis, Parrot syndrome, and Kaufmann syndrome, named after the German pathologist Eduard Kaufmann. Achondroplasia is the most common form of genetic short stature, occurring in 1 out of every 20,000 births. It is considered a rare disease. Achondroplasia is caused by a specific mutation in the fibroblast growth factor receptor gene FGFR-3. This gene is located on chromosome 4p 16.3. The mutation in achondroplasia leads to an overexpression of the FGFR3 receptor, inhibiting the proliferation of chondrocytes, which are cells responsible for cartilage formation. In 96% of cases, there is a specific G (1138) A point mutation in the FGFR-3 gene. Researchers are currently focusing on developing targets that can reduce the overexpression of the FGF3 receptor and inhibit chondrocyte formation. This mutation disrupts cartilage formation, causing the growth plates in bones to ossify prematurely. This results in restricted growth, particularly in the arms and legs, leading to a disproportionate short stature where the trunk and head are relatively longer than the extremities. This article provides an overview of achondroplasia, with a special focus on current therapies and future treatment options for pediatric patients. Various targets in the FGFR3 signaling pathway are being studied in clinical research, and their potential for treating achondroplasia will be analyzed in detail. The ultimate goal is to find a cure by targeting the aberrant excessive FGF3 receptor signaling pathways. The article will discuss the FGFR3 receptor pathways in detail and mention possible clues for curing the disease.