Abstract

Achondroplasia (ACH) is the most common pathology of the group of disorders called chondrodysplasias. It is resulting from a mutation in the Fibroblast Growth Factor Receptor type 3 (FGFR3) gene, one of the key regulators of endochondral ossification and it is characterized by different degrees of short-limb dwarfism. The mutation of the FGFR3 receptor, leads to an over-activated receptor, producing important changes at the intracellular signaling level. The most important changes are an accelerated rate of chondrocyte maturation leading to an altered extracellular matrix and an important modification in the biochemical behavior of the cells. Subsequently, terminal hypertrophic cells undergo accelerated apoptosis, which obstructs proper bone development and leads to the observed short stature phenotype. Even though, the molecular mechanisms causing the disease are known since 1994, there is no effective solution found yet, due to difficulties in the drug delivery phase but mainly because molecular events by which FGFR3 mediates its signaling are not completely understood. In this article, we review and discuss the latest patents in this field, with their corresponding literature, regarding future possible drugs for the treatment of this group of rare diseases. Some of these patents are concerning potential medicines that entered or are about to enter clinical trials and possibly will be succeed as future drug therapies.

Keywords: Achondroplasia, chondrocytes, chondrodystrophies, FGFR, hypochondroplasia, signaling pathways, thanatophoric dysplasia, tyrosine kinase.