Expanding horizons of achondroplasia treatment: current options and future developments

Activating mutations in the FGFR3 receptor tyrosine kinase lead to most prevalent form of genetic dwarfism in humans, the achondroplasia. Many features of the complex function of FGFR3 in growing skeleton were characterized, which facilitated identification of therapy targets, and drove progress toward treatment. In August 2021, the vosoritide was approved for treatment of achondroplasia, which is based on a stable variant of the C-natriuretic peptide. Other drugs may soon follow, as several conceptually different inhibitors of FGFR3 signaling progress through clinical trials. Here, we review the current achondroplasia therapeutics, describe their mechanisms, and illuminate motivations leading to their development. We also discuss perspectives of curing achondroplasia, and options for repurposing achondroplasia drugs for dwarfing conditions unrelated to FGFR3.