Thursday, February 1, 2018

Treating achondroplasia: sixth year online and news


Nine years ago, I was participating in a small online discussion group, in a time when blogs and social media were not yet as popular as now, and published a small summary of what I was reading about achondroplasia. 

At that time, having already talked with a number of investigators in the field and with a few representatives of advocacy groups I realized that the technical information and advances I was seeing in the literature were difficult to reach by the interested community. In that short article, my focus was perspective rather than reviewing what experts were doing already so well. I put together all potential strategies I found in the literature that could be used to treat achondroplasia in a few paragraphs. As most of the participants on that discussion group had no medical background I tried to use less heavy jargon and translate technical language to a more digestible vocabulary. I had hope.

That text received some positive feedback and was adopted by one of the advocacy groups. And was the seed for this blog.

That's it! Six years ago I started the Treating Achondroplasia blog to share what I was learning with all those interested in understanding achondroplasia and the ongoing work to beat the genetic mutation that leads to this skeletal dysplasia.

There are two kinds of articles published in the blog. The first type comprises reviews of the genetic disorder mechanisms and in the second there are those reviewing potential strategies. Nevertheless, I keep trying to mix both topics, to give a bit of background on the mechanisms involved in each strategy.

As of today, the blog has received more than 300K visits. When I review the statistics I can see that most visitors are more interested in the potential therapies and solutions for achondroplasia, so I think the blog is in the right track.

The blog has become a bit silent lately, as I mentioned in a previous article. And as I said then, this has more to do with my perception of a slight decrease in topics that may be interesting for the readers than for any other reason.

News, news, news

And, just to keep us on track and aware, I am happy to share with you that there is one more strategy that may become a strong option for the treatment of achondroplasia.

Just two days ago, a biotech venture called BridgeBio announced the establishment of QED Therapeutic, a new initiative to continue the research with BGJ398, a small molecule now called infigratinib, that was designed to block FGFRs, but which has more affinity with FGFR3. It was designed aiming to treat several kinds of cancer that use FGFRs to grow. To learn more about QED, visit their website here.

Infigratinib has been already tested in an animal model of achondroplasia and showed compelling promising results (1). This study leaded by Laurence Legeai-Mallet, a master in FGFR3-related dysplasias, was also reviewed here in the blog in 2016: Treating achondroplasia: NVP-BGJ398, a tyrosine kinase inhibitor, restores bone growth in a model of achondroplasia. This review starts with a tour through achondroplasia and the biology behind this skeletal dysplasia. It may help you to have a better view of the landscape (as I said, I mix topics...). 

In short, infigratinib was given in doses lower than those intended for the treatment of cancer, and basically was able to rescue bone growth in the tested model. It is important to note that, having already reached clinical trials for cancer, infigratinib showed a balanced safety profile. Now, it must be tested in the context of the developing body and the reason is simple. Although the molecule shows more affinity to FGFR3, it can also block other FGFRs, so we need to understand whether there would be safety issues in the developing organism exposed to infigratinib before it reaches the clinical development in children. If proven to be safe, then the rationale for its use would be strong as it directly targets the protein that causes achondroplasia compared to others such as vosoritide, that works indirectly.

These are exciting times. Some years ago, I heard from a renowned investigator that "in the near future the problem won't be to treat or not achondroplasia. The problem will be to decide which drug we will use to treat it". This will be true for the new generations.

Thank you

Thanks for your interest in the Treating Achondroplasia blog. I hope it keeps being useful for you!


1. Komla-Ebri Det al. Tyrosine kinase inhibitor NVP-BGJ398 functionally improves FGFR3-related dwarfism in mouse model. J Clin Invest 2016;126(5):1871-84. Free access.

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