Achondroplasia (ACH) is one of the most common skeletal dysplasias causing short stature owing to a gain-of-function mutation in the FGFR3 gene, which encodes the
fibroblast growth factor receptor 3. We found that
meclozine, an
over-the-counter drug for
motion sickness, inhibited elevated FGFR3 signaling in chondrocytic cells. To examine the feasibility of
meclozine administration in clinical settings, we investigated the effects of
meclozine on ACH model mice carrying the heterozygous Fgfr3(ach) transgene. We quantified the effect of
meclozine in bone explant cultures employing limb rudiments isolated from developing embryonic tibiae from Fgfr3(ach) mice. We found that
meclozine significantly increased the full-length and cartilaginous primordia of embryonic tibiae isolated from Fgfr3(ach) mice. We next analyzed the skeletal phenotypes of growing Fgfr3(ach) mice and wild-type mice with or without
meclozine treatment. In Fgfr3(ach) mice,
meclozine significantly increased the body length after 2 weeks of administration. At skeletal maturity, the bone lengths including the cranium, radius, ulna, femur, tibia, and vertebrae were significantly longer in
meclozine-treated Fgfr3(ach) mice than in untreated Fgfr3(ach) mice. Interestingly,
meclozine also increased bone growth in wild-type mice. The plasma concentration of
meclozine during treatment was within the range that has been used in clinical settings for
motion sickness. Increased longitudinal bone growth in Fgfr3(ach) mice by
oral administration of
meclozine in a growth period suggests potential clinical feasibility of
meclozine for the improvement of short stature in ACH.