Friday, May 30, 2014

FGF18, a key player for bone growth

There has been no major studies published lately in the specialized journals about therapies for achondroplasia and the blog slowed down a bit. Nevertheless,  during the last months several interesting studies have been published, exploring the physiology and mechanisms of cartilage and bone growth. One of them, a review about the fate of chondrocytes in the growth plate, authored by Pavel Krejci (1), an enthusiastic researcher of FGFR3 in bone development and cancer, we have already reviewed here

Now, I would like to highlight another interesting study published by an Australian group. If you are following this blog, you probably have already read about the main FGFR3 activators, FGF9 and FGF18 (2,3). In the new article, this group describes the presence of FGF18 and FGFR3 in the human vertebra and their influence in bone growth.(4)


Why is this relevant? Because it brings more evidence for the importance of FGF18 as a key player in cartilage development, a potential target for the treatment of achondroplasia.

Strategies to treat achondroplasia that instead of targeting FGFR3 aim their activators already exist, and one of them has received a lot of attention last year. I am referring to the strategy developed by the French group leaded by Dr. Elvire Gouze (5; reviewed here). In their study, they built a FGFR3-like molecule that is not fixed across the chondrocyte cell membrane like the natural receptor, so can circulate freely. They tested this compound in an animal model of achondroplasia and found that it was capable to rescue growth in the treated animals. 

The proposed mechanism of action of this compound is that it would be capable of capture the FGFR3 activators before they could activate the cell membrane bound receptor. In simple words, the compound was trapping the TV signals before they could reach the house antenna, so the TV didn't show any program. Don't feel puzzled with this text. Take a look in the review published here. It could help you to better understand the story.


1. Krejci P. The paradox of FGFR3 signaling in skeletal dysplasia: why chondrocytes growth arrest while other cells over proliferate. Mut Res 2013; 

2. Garofalo S et al.Skeletal dysplasia and defective chondrocyte differentiation by targeted overexpression of fibroblast growth factor 9 in transgenic mice. J Bone Miner Res 1999; 14 (11): 1909-15. Free access.

3. Davidson D et al. Fibroblast growth factor (FGF) 18 signals through FGF Receptor 3 to promote chondrogenesis. J Biol Chem 2005; 280: 20509-15. Free access. 

4. Shu C et al. Comparative immunolocalisation of perlecan, heparan sulphate, fibroblast growth factor-18, and fibroblast growth factor receptor-3 and their prospective roles in chondrogenic and osteogenic development of the human foetal spine. J.Eur Spine J 2013; 22(8):1774-84.

5. Garcia S et al. Postnatal soluble FGFR3 therapy rescues achondroplasia symptoms and restores bone growth in mice. Sci Transl Med 2013;5:203ra124.

Tuesday, May 20, 2014

Novas informações sobre o BMN-111

Na última conferência financeira, realizada em 14 de maio, a Biomarin divulgou algumas informações sobre o BMN-111. A conferência está disponível online no site da empresa. Para ouvir e baixar os slides, que estão disponíveis em pdf, você precisa se registrar antes. Os slides 7, 18 e 19 contem informações sobre o projeto do BMN-111. Comentários sobre o projeto estão no final da gravação da conferência.

Eis o link para a apresentação:
2014 Health Care Conference
BioMarin Pharmaceutical Inc
May 14, 2014 at 4:20 PM (PT)

Monday, May 19, 2014

News from Biomarin about BMN-111

Biomarin has posted slides from their last financial presentation (May 14th) at their website. There are three slides about BMN-111 (#7,18 & 19). The last one gives a glimpse about the ongoing phase 2 study design. BMN-111 news are mentioned in the end of the webcast.You can access it at the Biomarin website, but need to register first. 

This is the link for the presentation:

2014 Health Care Conference
BioMarin Pharmaceutical Inc
May 14, 2014 at 4:20 PM (PT)