Beyond Achondroplasia

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Talking with Prof.Matushita – Meclizine for achondroplasia head-researcher

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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.

matsu 1

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.

4 Comments

  1. Hola Inés como estas.
    Que buenas noticias las que nos cuentas.
    Esta es otra opción que nos llena de esperanzas.
    Dado que el Meclozine es un componente de venta abierta y que no genera efectos adversos, se puede considerar factible una aplicación actual en los niños con esta condición ?.
    Un gran abrazo y gracias por excelente información.

  2. Excelente questionamento Álvaro.
    Tenho uma filha com acondroplasia que tem 1 ano e meio e, desta forma, tenho acompanhado os estudos do BMN 111 (vosoritide), meclisina e também da estatina…

    Sobre o Vosoritide, já se divulga que eles irão, provavelmente em 2016, iniciar estudos com crianças menores de 5 anos e, os efeitos colaterais nas crianças que fizeram parte do primeiro trial, maiores de 5 anos, não foram significativos.

    No caso da meclisina e estatina, ambos são fármacos disponíveis atualmente. Fica então a dúvida quanto aos efeitos colaterais dos mesmos, principalmente em crianças em fase de formação não apenas óssea, mas de diversas outras coisas…

    O que me deixa ainda mais curioso sobre o caso é que minha esposa, durante a gravidez, fazia o uso de meclin (que tem a substancia meclizina), muito antes mesmo de sabermos da condição genética de nossa filha (só tivemos o diagnóstico quando ela tinha cerca de 2 meses de idade).
    Minha filha nasceu com 49cm e 4,5kg, que poderia ser considerado um padrão comum de tamanho. Logo após o nascimento, embora houvesse uma desproporção dos membros, fizemos uma consulta com uma geneticista que havia descartado o nanismo por julgar a desproporção “muito pequena”…

    Gostaria muito de saber as previsões de próximos passos para estes medicamentos, pois suponho que a disponibilização e acesso aos mesmos poderia ser mais rápido do que o BMN 111, principalmente aqui no Brasil.

    Um abraço a todos!

  3. Dr, Matushita mentioned that the experiments on dogs didn’t show as much of a result…. Dogs are probably more relevant to humans than mice are, because mouse bones are so small and highly vascularized. Did he ever mention releasing information on the dog studies? It would be important to know what the dog studies showed.

  4. Please let me know if Prof.Matushita or any others in case they had any progress since 2015 regarding using Meclozine in case of ACH.
    Thank you,
    Francesca

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