Decoy molecule stops dwarfism

A decoy molecule that blocks the growth-arresting process that leads to dwarfism has been developed by French researchers.

Dwarfism, known medically as achondroplasia, is a rare genetic disorder. Sufferers inherit a mutation in a gene called FGFR3, which encodes the receptor for one member of a family of growth signals called fibroblast growth factors (FGFs), which control the development of a range of tissues, including bones.

In the case of achondroplasia, the genetic mutation causes the receptor to become over-active, preventing bone-forming cells from developing properly so carriers are short-statured and at risk of a number of anatomical abnormalities and other health problems.

Now a team led by Elvire Gouze at INSERM - the national institute for health and medical research - in Nice, France, have developed a technique that appears to be able to reverse this situation, in mice at least.

Writing in Science Translational Medicine, and working with mice that develop the rodent equivalent of achondroplasia, the French team engineered a soluble FGF receptor which acts as a decoy, soaking up FGF signals so that far less reaches the mutant, overactive FGF receptor.

Administered as an injection twice per week for 3 weeks and beginning at birth, which is the period corresponding to the growing phase of the mice, the treatment produced animals with a stature and bone structure indistinguishable from normal healthy mice.

Examination of the organs and bones of the treated mice showed no abnormalities, and there were no obvious side effects when the treatment was given. Untreated control mice, on the other hand, were significantly smaller than their normal counterparts, had multiple bony abnormalities and a high mortality rate owing to their anatomical defects.

These are just preliminary results, and would need careful safety and dose testing before it could be translated to humans, which also have a very long phase of growth (almost two decades) compared with a mouse.

Nevertheless, this appears to be one of the most promising interventions yet developed for achondroplasia, which currently also leaves prospective parents in a quandary: should they have a child that will have a high likelihood of inheriting the trait?