Being the most recent collaborator of ALPE Foundation, I represented ALPE at the ICCBH 2015 in Salzburg. I had the opportunity to meet several researchers, doctors and patient groups, related to bone related diseases, metabolic, developmental conditions and rare skeletal dysplasias occuring in children.
During four of an engaging and relevant program, I had the chance to meet lots of people and hear about other conditions. It was very enriching and enlightening.
One of the persons I talked to was Prof. Masaki Matsushita, that is head researcher of Meclizine for achondroplasia. His team recently published:
Meclozine has a potential effects on short stature and foramen magnum stenosis in transgenic mice with achondroplasia.
He presented this publication refering meclizine as a potential treatment of achondroplasia, by drug re-positioning strategy (as already published here in Beyond Achondroplasia). He described the steps of his experimentation and he obtained impressive results. His team tested more than 1,300 existing molecules until they observed effective growth results in rats with mutation of ACH using meclizine.
After his presentation, I had an interesting talk with him and I asked some relevant questions. I asked about the side effects he had observing in the mice with ACH and he said he had observed no side effects. He referred that the LD50 (is the dose required to kill half the members of a tested population after a specified test duration. LD50 figures are frequently used as a general indicator of a substance’s acute toxicity. A lower LD50 is indicative of increased toxicity) was more than 200 times the administered dose, that it was of 0,4 mg/kg. (LD50 = 80mg/kg).
I also asked about the results he observed and he said the mice were treated for three weeks with 0,4mg/kg once a day, orally mixed in food, and the estimated annual growth rate he obtained was of 4 cm growth/year.
Recently BioMarin published a partial report of BMN-111 in clinical phase 2, with an estimated annual growth rate of 2cm/year.
Prof. Matsushita observed an increase in the global length (vertebrae in the spine) as well as the increase of the bone lengths of the radius, ulna, femur, tibia (arms and legs) and reduced bony bridges around foramen magnum (FM) in the mice treated with Meclizine.
The bony bridges around the foramen magnum are called syncondroses and are usually observed in achondroplasia. This reduces the diameter of the foramen magnum with the increased risk of medullar compression. So even a slight improvement at this point, is a very important one.
In conclusion, he observed restored proportionality in mice with ACH after 3 weeks of treatment with meclizine (the live span of a lab mouse is around 40 weeks).
His team also tested Meclizine in dogs, although this species showed less sensitivity to meclizine. Now, they want to take the next step to preclinical studies, for more research.
Thank you to Prof. Matsushita for his kindness and time for discussion his work.