For patients
There is no cure or specific treatment for achondroplasia yet. The available treatments try to address specific issues – symptoms arising from achondroplasia, and are targeted to alleviate the suffering of achondroplasia patients. For instance, antibiotics are given for ear infections or surgery may be performed in severe cases of spinal stenosis to prevent neurological impairment of walking ability or pain. Complex orthopedic approaches such as surgical limb lengthening may also be used, propagated by some specialists and criticized by others because of their serious complications, such as post-operative infection and higher incidence of fractures in lengthened bones. Some attempts to use growth hormone to increase the growth rate in achondroplasia were carried-out in the past, but showed minimal increase of skeletal growth.
In 2004, the advances in the understanding of the molecular mechanisms underlying the achondroplasia lead to the discovery of the inhibitory effect of a peptide (very small protein) named C-natriuretic peptide (CNP) on the FGFR3 signaling. CNP was no stranger to the bone biologists, since evidence of the pro-growth effects of CNP or other members of the natriuretic peptide family had been reported for some years. But the research published in 2004 was a true breakthrough. It demonstrated that the crossing of mice exhibiting elevated CNP levels with achondroplasia mice largely rescues the dwarfism. CNP was therefore a naturally occurring inhibitor of FGFR3 function in cartilage. Later studies elucidated the mechanism of the CNP-mediated effect on FGFR3 in cartilage and provided a basis for the development of a CNP-based approach to achondroplasia therapy. CNP is not very stable molecule and thus not practical for a long-term therapy. The initial stages of development were therefore geared towards creating a stable CNP analogue that would retain all the CNP’s features. Many other rounds of development followed at the Biomarin company located in San Rafael, California, leading to the molecule (BMN111 or vosoritide) which entered stage one of clinical testing for achondroplasia in 2012. vosoritide had now completed the clinical trials and shows very promising results. It is still not certain whether vosoritide will cure achondroplasia, but the prospect of doing so is now better than ever. Additional information on progress of vosoritide clinical testing can be found at Biomarin website.
At the same time, it is imperative that scientists continue researching novel ways to inhibit FGFR3. This is simply because that, as with any drug, there is a risk that vosoritide will not be fully effective as an achondroplasia treatment, for instance because the patients will gradually become resistant to it. If we stop the research now, we may come up empty handed many years later when we might need an alternative to the vosoritide for achondroplasia therapy. Please see the ‘Research’ section of the web for updates on recent research concerning novel avenues of FGFR3 targeting as well as the progress of vosoritide clinical trials.