Researchers identify protein as a possible cure for dwarfism

As a child's bones grow, cartilage cells in the bone – called chondrocytes – mature and die, allowing hard bony material to be deposited at the site. Sufferers of achondroplasia, the most common form of dwarfism, have inherited a mutation in a gene called FGFR3, which provides instructions for making a protein involved in bone tissue formation.

The faulty protein causes the cartilage cells to be overstimulated by growth factors and stops the chondrocytes from maturing. Bone formation is prevented and the long bones in the body do not extend as normal – leaving those with the condition short in stature. They can also suffer associated problems. These include curvature of the spine, and difficulty with breathing and hearing.

Working in the EU-funded GeneCellTher project, a team of scientists at France’s Institut National de la Santé et de la Recherche Médicale (INSERM) developed a decoy protein to prevent the mutation from arresting growth.

The irony is that the root of the problem – a lack of growth – lies with too many growth factors stimulating a child's bones. The project’s solution is to mop up the excess factors with a molecular decoy.

Marie Curie fellow and senior GeneCellTher researcher Elvire Gouze of INSERM explains: “There is a flaw in a receptor and the stimulation by the growth factor lasts longer. Eventually, the bone forms but the bones are shorter.”

When injected into mice with the equivalent of human achondroplasia, the project’s protein, ‘soluble FGFR3’, stops enough binding at the mutation so normal growth can resume and be restored, the researchers found.

Moreover, other associated conditions disappeared in the test mice – such as fluid build-up around the brain and curvature of the spine. Bowing of the spinal column in the test mice was cut from 80% to 6% depending on the dose.

“We suppressed complications,” Gouze says. “The test mice don’t have breathing problems and they can move around normally.”

Significantly, there were no signs of short-term toxicity caused by the injections. As the treated mice matured, they were fertile and had normal pups.

Future treatment?

Gouze stresses that the GeneCellTher protein is still in the early stage of development for use as a potential treatment for achondroplasia. The project ended in October 2013 and its researchers have filed a patent for the protein it developed.

They have also established a small company, TherAchon, to further develop the soluble FGFR3 protein. As part of the development, the company is working out the optimal dosage and making absolutely sure that there are no unwelcome side-effects before applying for approval to test it on humans as a potential treatment.

“Mice have no puberty,” comments Gouze, “and the human growth period extends over almost two decades compared with a mouse. The treatment would be administered as soon as the mutation is identified. This has to be before puberty when other hormones start to have an effect on growth.”