Treating achondroplasia with peptides specifically against FGFR3

The Yissum Research Development Company of the Hebrew University of Jerusalem is looking for cooperation to further develop the strategy they created to block the fibroblast growth factor receptor type 3 (FGFR3) activity in achondroplasia.

For more information visit: http://www.ittn.org.il/technology.php?tech_id=61365

Peptides are short chains of amino acids which may possess, like the larger relatives proteins, specific chemical properties which in turn can trigger or block certain reactions in cells. In this case, the researchers pledge they developed a series of peptides with significant specificity for FGFR3. With high affinity for this receptor they could bind to it and block its activity.

I couldn't find any publication about this strategy, but there are similar approaches being explored by other groups, as you can see visiting this previous article of the blog.

New perspectives, new challenges

The peptide concept is interesting, however there is a number of natural questions that we should make:

First, are these peptides specific enough to work only against FGFR3? We must remember that FGFR3 has three sister proteins, all sharing great homology (have similar chemical parts inside their structure). Specificity is a must have. We don't want to block other enzymes in a child with achondroplasia.

Second, chemical affinity is fundamental, but we need to learn if they would work both directly in cells (in vitro) and in living models (in vivo). Some strategies may work in vitro but may fail in vivo.

Third, peptides are natural victims of specialized blood, tissue and cell enzymes (peptidases) which deactivate them. This means that it is unlikely they could be given naked (without protection), so they would need a carrying system or a protected chemical structure. You certainly remember CNP is a peptide. The CNP analogue BMN-111 is a peptide which has been developed to resist more time to the action of those enzymes (reviewed here). So, a good question for someone developing peptides is how they would be delivered to the growth plate and the chondrocytes. We have also reviewed this topic in this article of the blog. Nevertheless, recently published studies describe different methods to help fragile molecules to reach the bone and I plan to write a note about them soon.