A team of French researchers has developed a treatment capable of stimulating normal growth in mice and, thus, eliminating the symptoms of the most common form of short-limbed dwarfism. The highly encouraging results of the INSERM research bring new hope for an eventual human application.
Achondroplasic dwarfism is a genetic disorder of bone growth. It concerns 1 out of 15,000 births. The patients present average-sized torsos and short limbs and may suffer serious additional symptoms such as respiratory difficulties (sleep apnea), handicapping malformations, pressure on the cranium and even paraplegia. These symptoms originate from a mutation of the FGFR3 gene, which prevents it from efficiently playing its role in the mechanism of transforming cartilage into bone.
A mouse model of achondroplasia (Source: Weizmann Institute of Science)
“The concept of the treatment is very simple,” explains Elvire Gouze, co-author of the study. “What it does is fool the mouse’s body.” The FGFR3 gene produces a protein receptor of the same name, important for regulating growth. Dysfunctional copies of the receptor result in dwarfism. In the treatment under study, mice with the same mutation as causes human achondroplasy were injected with functional human FGFR3 receptors. These working copies of the receptor replace their mutated counterparts and re-establish the balance that enables the bone to develop at a normal rate.
The mice receiving the FGFR3 protein made impressive recoveries. In only three weeks (equivalent to reaching adolescence in humans), they grew to the same size as the other mice and all symptoms disappeared.
The shape of the head changed, the breathing observed was easier. Particularly representative of how efficient the protocol turned out to be, the treated mice were able to give birth to more pups than before. The reason for this is that their pelvis widened, proof that the bones of the limbs were not the only ones to respond to the treatment.
Stéphanie Garcia (left) and Elvire Gouze, co-authors
of the study on restoring bone growth in mice with dwarfism.
“We are quite confident that this research can be applied to humans,” says Elvire Gouze. However, “the mouse model has its downsides, it is in no way sufficient.” Before a human treatment can be imagined, trials on other animals, and then humans, need to be done. The research will most likely continue for another 3 to 5 years.
One of the crucial differences in transposing the treatment to humans is that, unlike mice, human growth stops after puberty. Mice continue to grow all their lives and, so, the treatment can be provided to them at any time (Technically, if the injections were to be given to the rodents for longer than necessary, they could become giant.) In the case of humans, the treatment would imperatively have to be given at an early age. Whether it be while the patient is still a baby or before the end of puberty is yet to be determined.
Ethical issues could arise from the need to deliver the treatment to minors, which implies that someone other than the patient would have to take the decision. Dwarfism only impacts physical characteristics, and not intellectual ones. In this sense, it cannot simply and solely be considered a genetic disease. It constitutes, for some individuals, a question of identity. “In a forest, there are big trees and there are small trees,” points out Patrick Petit-Jean, president of the French Association of Little People (APPT), “I know a number of people who are very attached to their identity as little people.”