During the 7th International Conference on Children's Bone Health, which took place last week in Salzburg, Austria, the Japanese group working with meclizine (or meclozine) has presented new results of their continuing work to explore this drug for the treatment of achondroplasia.
Normally, Investigators presenting their work in scientific meetings do not have space to publish all results of their study in the meeting abstract, so the information here is limited to what has already been divulged. We can expect that a complete description of their work will be published later in 2015.
Research
According to the meeting abstract (1), Matsushita and coworkers performed several complementary studies. They developed a mouse model of achondroplasia and gave, to growing animals, food containing meclizine during three weeks. They noticed that all long bones and vertebrae in the treated animals grew significantly more than in the control group. However, they did not observed differences in the foramen magnum. Early closure of the cranial sutures are considered a typical characteristic of achondroplasia and the reason for foramen magnum stenosis and other neurological complications (2,3)
They also gave meclizine to pregnant mice and studied the synchondroses (the cranal sutures) around the foramen magnum and found that maternal administration of meclizine reduced the bone bridge formation in that region, meaning that meclizine was able to retard the synchondrosis closure in the treated newborns.
We will need to wait for the complete results to better understand the tests and their results. For instance, the abstract does not mention safety information about giving meclizine to pregnant animals. However, this is the first time a drug, administered to pregnant animals, is being described as having positive influence in the growth pattern of the foramen magnum in achondroplastic animals, putting meclizine as potential candidate for very early therapy in achondroplasia.
What is the implication of these preliminary tests with meclizine for the real life?
If meclizine is proven to have safe positive effects in retarding the cranial sutures closure in utero, in achondroplasia, this could be a breakthrough step in order to reduce or mitigate the common neurological complications seen in newborns and infants with achondroplasia. From another standpoint, it seems that meclizine could also be tested in models of craniosynostosis, such as Muenke Syndrome, which is also caused by a mutation in FGFR3.
To learn more about meclizine, you can visit these previous articles of the blog (they also contain the references for the original studies):
- Meclizine / meclozine for achondroplasia? (11/12/2013)
- Treating achondroplasia: where we are now (18/06/2014)
- Treating achondroplasia with meclizine / meclozine (15/12/2014)
References
1. Matsushita M et al. Meclozine has a potential effects on short stature and foramen magnum stenosis in transgenic mice with achondroplasia. Bone Abstracts (2015) 4 OC13 | DOI:10.1530/boneabs.4.OC13. Free access.
3. Di Rocco et al. FGFR3 mutation causes abnormal membranous ossification in achondroplasia.Hum Mol Genet. 2014;23(11):2914-25. Free access.
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