At 9 years old, Amandine is the first child in France to receive a new drug against achondroplasia, the most common form of dwarfism. The discovery of the gene responsible for this disease and the molecule tested is the result of French research at the Necker Parisian hospital.

Laurence Legeai-Mallet wouldn’t have missed it for the world. On Tuesday, March 30, she was at the side of Amandine, 9 years old, the first patient in France to receive a new drug against achondroplasia, the most common form of dwarfism. « From bench to bedside », as they say in scientific jargon: from the laboratory to the bedside! The researcher has a long history with this disease. It was in 1994 that she co-discovered at the Necker hospital in Paris that FGFR3 was the gene responsible for this anomaly affecting the growth of bones and their cartilage.

« Before thinking about treatment, we had to understand what was dysfunctional, » she explains. Twenty years of research, developing models… And, in 2014, bingo, the intuition that infigratinib, a molecule then used against bladder cancer, could block the activity of the gene. Patented in France, the therapy was bought and developed across the Atlantic. In July 2020, an international trial began: a child was treated in Australia, with preliminary results expected in the coming months.

In France, with Necker and the Imagine Institute for genetic diseases, Amandine is the first child to benefit from this procedure before being followed soon by a little boy. The goal is to gain 10 to 20 cm. This advance is the result of French research, » says Geneviève Baujat, a pediatric geneticist. The molecule, which acts like a key in a lock, is a real hope. But be careful, it is not a magic wand against the disease. Its good tolerance will be our compass.  »

Other molecules under development

Several other molecules are also in development, including one from the manufacturer BioMarin that could lead to a marketing authorization application. And so much the better, because achondroplasia is not « just » a problem of small size. It leads to orthopedic, back and ENT complications, not to mention the social handicap.

If the results of the trials are up to par, several hundred children could ultimately be eligible to receive this – or even these – molecule. « Nothing is taboo, » says Dr Baujat, « including extending treatment to adults with achondroplases who suffer from complications such as sleep apnea or hearing problems. We will move forward, slowly, but surely.  »

Source : Le Parisien, article by Florence Méréo, April 9, 2021 

The hope of Amandine, 9 years old, the first child in France to test a new treatment against dwarfism.

EXCLUSIVE: This little girl who suffers from achondroplasia, the most common form of dwarfism, is receiving a drug designed to « break » the action of her defective gene as part of a clinical trial conducted by the Necker hospital and the Imagine Institute. She hopes to grow a few more centimeters.

Finally, it is the embroidery on the collar of her blue dress that best sums up Amandine. « Happy ». At nine years old, the little girl confirms it with a big nod of her head: « Oh yes, yes, I am very happy. I have just received a treatment that will make me grow a bit. Not totally, but I hope by several centimeters, » she explains, with a maturity that makes us forget her blond hair, her childish face and her 1.03 meter stature that she takes the trouble to straighten regularly. At her age, children are on average 30 cm taller.

An uncle of 1.95 m, a father of 1.87 m, a mother of 1.69 m… That Amandine was born with achondroplasia was almost a feat. This genetic disease, which affects 2,400 people in France, including the actress Mimie Mathy, may be rare, but it is the most common form of dwarfism. It is an anomaly that affects the growth of cartilage, particularly in the limbs. « In fact, from my neck to my pelvis, my bones grow well, but those of the arms and legs have difficulty, » she describes.

« Each centimeter gained is a victory »

But for the last ten days, in her house in Rouen (Seine-Maritime), Amandine has been swallowing seven granules every morning dipped in her compote. As we reveal, she is the first child in France to test a new drug, as part of a clinical trial conducted by the prestigious Necker Parisian hospital  and the Imagine institute for genetic diseases . « And the thirteenth in the world! « she says. With a knowing hazelnut look, she agrees with Pascal, her father : one, thirteen, all lucky numbers!

The first night after the treatment, Valerie, his mother, was awakened by anxiety. But then the optimism characteristic of this close-knit family took over. Infigratinib – that’s the name of the molecule tested – « is a chance, » she says. « The only one given to Amandine to grow up. It is not miraculous, it will not cancel the disease, but it will help her: each centimeter gained is a victory. « If the promises become reality, « a gain of 10 to 20 cm would be great, » notes researcher Laurence Legeai-Mallet, while the average height of women with achondroplasia is 1.24 m in adulthood. « In any case, to be 1.90 m tall, no thank you, » warns Amandine with a smile. In this case, the medication, which she will take for at least two years, is designed to « break » the action of the defective gene.

Because achondroplasia is not just, as Valerie and Pascal first thought, « having a little girl and then that’s it. « No, they received other « hammer blows »: a risk of compression of their child’s skull and spine that had to be closely monitored, back problems that caused Amandine to wear a corset until the age of three, and a diet she had to follow. No meat in the evening, lots of vegetables, » says the fourth grader. But I’m allowed to let myself go. At Easter, my basket was so full that it broke, I just have to eat the chocolates less quickly than the other children.  »

Archaeologist or star dancer

Obviously, there is the social gaze, the reaction of others. « We’re apprehensive about going to school, » concedes Pascal: how will Amandine be received? Will the school be as exemplary as the current one, which has installed toilets, a sink and a blackboard adapted to her size?  » That’s the next chapter, Dad, says Amandine. For the moment I’m enjoying it!  » As bubbly as determined, the little girl insists:  » I would like to say that I support other people who have the disease and can not have this medicine.  »

Source : Le Parisien, article by Florence Méréo, April 9, 2021