[Application of disease-specific iPS cells for intractable diseases-from pathomechanisms to drug discovery].

Abstract

Genetic diseases affecting bone and cartilage, which are main components of the locomotive system, are extremely diverse. Even if the causative genes are known, detail pathomechanisms are not yet disclosed in most of them and no effective treatments are established. One of such condition is fibrodysplasia ossificance progressive, which is characterized by systemic ectopoic bone formation and caused by mutations of ACVR1/ALK2 gene encoding one of typeⅠBMP receptors. Using patient-derived iPS cells, we have succeeded to recapitulate the disease in vitro and found a unexpected molecular mechanism that Activin-A induced the BMP signal through mutant receptors. This novel finding provides us with a key to discover drugs for this condition.