Drug to treat common type of dwarfism

Melbourne: A ground-breaking drug that helps regulate bone development may boost growth rates in children with achondroplasia -- the most common type of dwarfism -- according to scientists who conducted a global trial.

The drug vosoritide was tested in children aged five to 14 years, according to the research published in the New England Journal of Medicine. According to researchers, achondroplasia is caused by overactivity of a signal that stops growth and could be likened to overwatering a plant.

"This drug basically kinks the hose so that the plant gets the right amount of water and can resume regular growth," said Ravi Savarirayan, a professor at Murdoch Children's Research Institute in Australia. Achondroplasia is a genetic bone disorder affecting about one in every 25,000 infants. It is caused by a mutation in the FGFR3 gene that impairs the growth of bones in the limbs, the spine, and base of the skull.

The most common health complications experienced by children with achondroplasia are spinal cord compression, spinal curvature and bowed legs. About half of these children will need spinal or other surgery. "This can mean a lot of time away from school as the child recovers and rehabilitates after surgery, which can affect important social connections," Savarirayan said.

Unlike other treatments – such as growth hormone and limb-lengthening surgery – that focus on symptoms, vosoritide focuses on the underlying cause of achondroplasia and directly counteracts the effect of the mutation that slows growth. The study ran over four years across research centres in Australia, France, the UK and the US with 35 children assigned to one of four groups receiving daily subcutaneous doses of the drug in increasing amounts.

The patients' average boost in height to about six centimetres per year was close to growth rates among children of average stature, and the side effects of the drug were mostly mild, said Julie Hoover, an associate professor at the Johns Hopkins University in the US. "Right now, the results of the study show an impact on growth, and this effect is sustained, at least over nearly four years in this trial," Hoover said. "The potential long-term benefit will take more time to observe," she said.

The main aims of the trials were to evaluate the safety and tolerability of the drug and to determine the best dose for the Phase 3 trials, which are now underway. The results showed vosoritide was generally well tolerated by patients and demonstrated dose-dependent increases in centimetres grown per year during the first six months, with improvements maintained over the study extension period of a further three years.

On average, participants in the trial grew at a 50 per cent faster compared to baseline with no adverse effects on body proportion. Overall bone age was not accelerated implying that this effect, if sustained long-term, might increase final adult height.

"This study is the very first report of a possible disruptive, precision therapy for children with achondroplasia, which we hope will improve their health outcomes and functioning, as well as increase their height and access to their environment," Savarirayan said.