Beyond Achondroplasia

Growing together with Clara

Achondroplasia highlights


During three full days, the V International Congress around Achondroplasia and other Skeletal Dysplasia took place in the north of Spain, very well-organized by Alpe Foundation. Several world-renowned experts attended, giving one or more lectures, over 500 people registered, mainly parents of children with achondroplasia and more than 140 children with skeletal dysplasia with a few months of age to 14-15 years-old were present. The attendance of adults with skeletal dysplasia was significantly low.


Dr. William Mackenzie surrounded by several children and parents. Picture kindly provided by Vitor Sobral Monteiro            14 Oct 2014

Several lectures in highly relevant medical themes for achondroplasia were presented by some of the most well-known specialists around the worlds and I have to mention Prof. Lachman lecture, an expert in skeletal dysplasia radiologic diagnosis, who opened the congress. Dr. Fernando Molina Montalva, an incredible expert in maxilofacial and plastic surgery. At the geneticists level, attended Dr. Karen Heath, a senior researcher at the INGEMM, Madrid, and Dr. Sérgio Sousa, a medical geneticist at Coimbra Pediatric Hospital, with relevant studies in major international skeletal dysplasia research centers. Two incredible lectures were given by Dr. William Mackenzie, an amazing orthopaedist with substantial experience in skeletal dysplasia, limb length discrepancy, limb alignment and muscle disease.

Dr. Elvire Gouze, working at INSERM, attended the congress too. She is expert in gene and cell therapy for musculoskeletal disorders and she is responsable for the team that developed the soluble FGFR3. In my opinion, this could be a valid therapy, and although I wrote that it is missing a pharmaceutical company to take it over from here, Dr. Elvire Gouze was kind to write to me, after reading this post, for a rectification.

Dr. Gouze funded TherAchon (Therpeutics for Achondropalsia) financed by Versant Ventures and Inserm Transfert Initiative. So they have fundings to take the study to the next step. This team goal is to do all the preclinical development of the soluble FGFR3. They are aware of the difficulties of this challenge but they are doing their best to develop a molecule with great outcome for achondroplasia. So they are reviewing the soluble FGFR3 in the way to make it work better and be even more effective. I will keep following closely Dr. Gouze work, since I believe the soluble FGFR3 has a major chance of having a real physiologic success in treating achondroplasia.

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 Between so many outstanding presentations, I have to highlight two:

1) Dr. Paley intervention in limb lengthening. He explained the meaning for bone distraction and bone consolidation, and the timeline he adopted for the all process. Essentially, he introduced a new limb lengthening technic, the PRECICE 2, based on a magnetic interaction between the PRECICE intramedullary nail and remote control. This nail goes inside the bone to length and grows inside the bone after this has been cut during surgery.

This process allows a precision controlled distraction phase (when the two pieces of bone are getting apart) with the ability to noninvasive customize treatment. The consolidation phase, when bone starts to grow in the open space between the two bone pieces, takes the same time as the distraction phase take. Major advantages: precision, recovery time, less infection rates and no exterior devices or scars. This is a highly significant change in the way lengthening are done from now one.

I predict that in a couple of years, this technique will be available in most public medical hospital around the world, once at Paley Advanced Limb lengthening Institute, the price for a double femur and tibia lengthening surgery can have a cost of 170.000 USD. Not including the price of the surgery to remove the nails. And two more surgeries have to be done for a child with achondroplasia, with the wish of lengthening.

I´ve discovered that by now, the PRECICE technique is in current use at the Royal National Orthopaedic Hospital,  NHS trust, for that, a public institution, at Stanmore, Middlesex, England.

In the case of European community rights and rules, patients of EU countries can attend to medical advance centers all across Europe, if the intervention/surgery in need is not available in the public hospitals of that person country. Specific rules applied for each case.

There is at this point an open clinical trial for PRECICE 2: Post-Market study of the Ellipse PRECICE intramedullary Limb lengthening System (PINS) and this study is currently recruiting participants.

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2) The other major intervention, and for me the most relevant of all, was Dr. Yayon lecture.

He is a well-known scientist that dedicated almost 20 years to study of FGF´s, FGFR3 and the growth plate, with more than 100 papers published. The first article I found published by him was from 1995: Identification of fibroblast growth factor 9 (FGF9) as a high affinity, heparin dependent ligand for FGF receptors 3 and 2 but not for FGF receptors 1 and 4. Since then, he persisted in the research about the growth plate, mainly in one direction: to disclosure a treatment for achondroplasia.

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He was the first researcher of the CNP back in 2003. Now it belongs to BioMarin with some changes and under the designation of BMN-111.

In his research, the CNP had a 2 minutes half life (the quantification of half of the time the molecule is circulating in the body before being “destroyed”). So BioMarin bought the patent from Prof. Yahon and increased its stability to a 45 minutes half-life.

Question: will be enough for children to have BMN-111 acting in their growth for 45 minutes per day? And at what time it will be given? During day or at night, when the growth hormone is secreted?

Well, I was introduced to him by Carmen Alonso, from Alpe, during one of the social moments of the congress and we had a very interesting conversation around the latest discoveries around achondroplasia. He revealed the next day in his lecture our talk.

Prof. Yayon mentioned several research works he made around treatment for the over activation of FGFR3 and he disclosure his lastest work: FGF18v1. It is know from some years now that FGF18, that activates FGFR3, regulate proliferation, differentiation, and matrix production of articular and growth plate chondrocytes in vivo and in vitro. FGF18 signals through FGFR3 to promote cartilage production by chondrocytes.

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Lets wait for further developments of this study!

Searching for FGF18v1, I found Prof. Yayon latest patent: Treatment of achondroplasia with encapsulated cnp-secreting cells, published less than a month ago (18 Sep 2014). I will come back to this later.

For a lot of people who attended the congress, the most expected lecture was by Dr. Mirko Essin, Head of Medical Affairs EUMEA, BioMarin Europe Ltd. I was presented to him in a social event and he was very nice to talk to. Besides that, I think most people were disappointed with his presentation once it was mainly a description of BMN-111 and the clinical trial design. This were two very interesting subjects, but people were expecting to hear other things beside that. By his words, BMN-111 won´t be ready for distribution before 2018.


Over all, I want to thank deeply to Carmen Alonso, Fani and Cristina for their incredible work and extraordinary dedication in the organization of the congress and to the quality and quantity of experts in achondroplasia they could get together for this event. Thank you!


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