Highlights of the ISDS 2017 meeting

The International Skeletal Dysplasia Society meeting held in Bruges 

received more than 250 attendees from the 5 continents most of them were geneticists working on rare bone diseases.

Representatives from companies that are currently working in the development of a medicine for achondroplasia participated in the meeting, namely BioMarin, Therachon and Ascendis Pharma. 

Therachon was represented by the new Chief Medical Officer, Christian Meyer, as also my Maarten Kraan, adviser, Luca Santarelli, CEO and Elvire Gouze, head researcher. BioMarin was represented by Paul Humphrey, Associate Director for Patient Advocacy in EU and a Charlotte Roberts, Senior Manager for Patient advocacy. Ascendis Pharma was represented by Dorthe Viuff, Global Project Director.

The only company of these three that did a presentation was BioMarin, but with no data from any study. Also Dr. Ravi Savarirayan, from Murdoch children's Hospital, Melbourne, Australia, did a review presentation on the current status of the emerging therapies for skeletal dysplasias in clinical trials and practice, including some lines about the C-natriuretic peptide in achondroplasia and future potential targeted therapeutic options, but with no new information on the clinical study ongoing.

Dr. Julie Hoover Fong presented an ongoing multicentered study on achondroplasia to observe which adverse health outcomes from patients with achondroplasia related to cardiovascular disease, pain, compromised physical function and obstructive/central sleep apnea.

Once the natural history and risk factors are poorly understood in order to better define the natural history of achondroplasia and understand the health outcomes of past and current medical and surgical practices, Julie HF is conducting a large multi-center registry with a retrospective and prospective functionality with the contribution of 5 clinical centers in the USA.

Also, Dr. Kitoh from Nagoya Universite did a presentation. He is one of the researchers working on Meclozine, from Nagoya University, Japan, and in his presentation, he showed that the body lengths of mice with achondroplasia (Fgfr3ach mice) were increased by oral administration of 1 or 2 mg/kg/day of meclozine as also the bone volume and trabecular bone quality.

Dr. Kitoh ended concluding that the team still needs to study toxicity and adverse events associated with long-term administration and they are aiming to start a clinical trial in Japan with 12 children with ACH in the next months. These studies: phase 1 and 2 trial will be conducted in Japan.

 

But one of the most relevant highlights of the ISDS was a study presented by Celine Saint-Laurent, one of the young researchers working in Elvire Gouze´s team (iBV, Therachon). Celine studied the link between the FGFR3 mutation and the metabolic complications related to achondroplasia. In parallel to this study, Celine studied the retrospective data from children and adolescents with achondroplasia, measuring several parameters and compared between three age groups: [0-3], [4-8] and [9-18] years old.

In this study with a mouse model with achondroplasia, Celine injected ACH mice with Flag-sFGFR3 during the growth period and could confirm that the bone growth was restored and the metabolic deregulations were corrected with the administration of this compound. With this study, Celine concluded that the metabolic disturbances in achondroplasia patients are not associated with classical obesity complications, as diabetes and that sFGFR3 proved to be a promising treatment for achondroplasia restoring bone growth and also in preventing the metabolic deregulations and the development of obesity.

Florence Authier, also a Ph.D. student from the Elvire Gouze team presented a study on the application of a technique with near-infrared imaging to assess longitudinal bone growth velocity.

In this presentation, Florence showed her studies on the development of in vivo methods for measuring skeletal growth at the early stage of the condition This is crucial for characterization of animal models for skeletal dysplasias once the skeletal growth assessment in juvenile animals is generally performed on long bones or full body length measurements at termination, providing endpoint values and requiring analysis of large cohorts of animals. This process can be very stressful for animals. This technology could be used for the study of early bone development in animal models for skeletal dysplasias and evaluate potential therapies.

Martin Duplan, another young researcher from INSERM Paris and member of the research team led by Laurence Legeai-Mallet conducted a comparative analysis of specific mouse models and concluded that FGFR3 mutation, beyond affecting chondrocyte differentiation and multiplication, also interferes with the differentiation of osteoblasts in the growth of the long bones and craniofacial skeleton as in bone mass acquisition during endochondral and membranous ossification. The researcher concluded that abnormal osteoblast differentiation could contribute to the defective ossification observed in Fgf3-related disorders.

Overall, this was a very informative meeting and interesting presentations, related to several skeletal dysplasias. The next ISDS meeting will be held in Oslo, in 2019.