Putting An End To One Type Of Dwarfism

Achondroplasia, a type of dwarfism, is a rare genetic disorder characterized by short limbs, a normal-sized torso, and a slightly enlarged head. In severe cases, deformations in the head and spine can lead to serious medical complications. The condition is a result of a single mutation in the gene coding for fibroblast growth factor receptor 3 (FGFR3), a protein that is part of a signaling cascade that eventually results in certain cells being replaced by bone. FGFR3 binds to and is activated by the protein FGF, but the mutation alters FGFR3 and slows elimination of the FGF-FGFR3 complex, causing a detrimentally prolonged signal that delays maturation of the cells. Elvire Gouze of the French National Institute of Health & Medical Research and coworkers developed a soluble form of FGFR3 to act as a decoy for FGF. In mice engineered to have achondroplasia, postnatal injections of the decoy resulted in normal stature and a significant decrease in other complications (Sci. Transl. Med. 2013, DOI: 10.1126/scitranslmed.3006247). The researchers observed no signs of toxicity or ill reproductive effects. The team hopes the approach can eventually be used to treat human patients to normalize bone growth.