It can be said without fear of being wrong that the Avner Yayon team at the Israeli Biotech company Prochon is leading the world’s research on achondroplasia, the most common cause of genetic dwarfism. The birth of a child with achondroplasia is at the origin of this company. The father of that girl, a doctor of Jewish origin, focused his efforts on breaking indifference which, up until that moment, the study of this genetic illness had received. He founded Prochon and let Yayon take over. In a little over ten years, he hasn’t just contributed decisive knowledge about achondroplasia, but also has laid the groundwork to someday give possible therapeutic solutions.

A symbol of the scientific power of the team that Yayon directs, and the philosophy which moves them are their mice. In laboratories all over the world, work is carried out thanks to Prochon sending them rodents. What is it with these mysterious mustelids? Yayon has managed to create a line of laboratory mice which incorporate the achondroplasia mutation; it’s thanks only to them that they’ve been able to experiment on possible solutions in several centres, including Spanish Universities, such as the one in Santiago.

The expert was in Gijon a few days ago, invited by the Alpe Foundation, which is a Spanish organisation chaired by one of the fathers of Prochon, the British doctor, Phillip Press. Yayon exhibited there the spirit of his work: “One of our goals is to collaborate with different governments, with the large parmaceutical industry, with researchers, universities, non-governmental organisations.”

Hope for those affected.
The mouse, of course, is not the only achievement of this young biotech company, which is vanguard and a pioneer in its works, but modest compared to the powerful multinationals of the pharmaceutical sector.Since its inception, it has obtained almost miraculous results that shook the community affected by achondroplasia, in particular, many parents, who saw with hope that there was the possibility of a solution for these children.

“At the end of 1996, we discovered which protein starts the signal in the particular receptor (the FGFR3) and we also discovered the molecular process. We also managed Promabin, an antibody which was very promising in the study of in-vitro cells. Those were times in which we were all very optimistic about the company. But then there came the moment when you realise that although you have a good component, things aren’t so easy”, the expert remembers. And he said: “The process of achondroplasia takes place in one of the areas which the body most needs, the area of bone growth. When a live being grows, even in practical absence of food supplies, the animal keeps growing. I compare it with other very preserved areas, such as the brain. It’s very difficult to achieve a compound which gets there. That’s why, although we obtained a very efficient antibody, we have seen that getting to the growth plate of the bone is very hard. It is not impossible, but the complexity of achieving it is extreme”.

Where does this complication lie? In addition to the jealous resistance of the body towards having the vital processes altered, there is a sizable question that is important, above all, because it is a poorly irrigated area. Here the magnitudes are measured in daltons (one dalton is equivalent to the size of a hydrogen atom). “The molecule of our antibody measures 150 kilodaltons. We have been able to refine it, to leave it in the third part. Our hope now is to collaborate with a Swedish company that has discovered an antibody six kilodaltons in size.”

Achondroplasia is the most common form of dwarfism of genetic origin. It causes not just short height -normally between 120 and 130 centimeters in height in adults- but also very short arms and legs, a relatively large head with a prominent forehead, hands in a trident shape and all kinds of medical problems, such as marrow compression, severe spine disorders, respiratory and auditory disorders, etc. One case in every 15,000 births is registered and the majority of them come from spontaneous mutation, meaning that their parents don’t suffer from it.

Until a few years ago, there was another frequent kind of dwarfism, pituitary, caused by a growth hormone deficit, which provoked people of very short size, but with no disproportions. The synthesis of this hormone and its incorporation into the battery of available treatments has made this type of dwarfism curable in a very satisfactory way. However, against achondroplasia, surgical lengthening in young children is today the only palliative technique which medicine offers for the many problems of achondroplasts – daily life, image, architectural barriers, personal autonomy and even hygiene. The technique is very hard: It involves breaking the bones which need to be lengthened in an operating theatre, so that they can later be forced, via tensioners, to start creating a callus around the fracture. It’s a painful and complex process, in which millimeters per day are cut and which can take almost two years in a key moment in the development of children, because it has to be carried out at around 12 years of age for those affected.

Yayon also hopes that in this case, they are very close to using in humans: “We have developed a process to accelerate the process of callus generation with stem cells, and with this we hope to be able to shorten substantially the duration of this process and of any other type of complex fracture”. This is a system that is parallel to another one that is being developed by the company -the Biocart II, patented and in a very advanced stage- for achieving the regeneration of damaged cartilage. “We are realistic, we have learned a lot, but we still have a lot to discover”, Yayon admits, with less false modesty than the seriousness of a man of science.

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