Systemic Administration of C-Type Natriuretic Peptide as a Novel Therapeutic Strategy for Skeletal Dysplasias

Endocrinology - Tập 150 Số 7 - Trang 3138-3144 - 2009
Akihiro Yasoda1, Hidetomo Kitamura2, Toshihito Fujii1, Eri Kondo1, Naoaki Murao2, Masako Miura1, Naotetsu Kanamoto1, Yasato Komatsu1, Hiroshi Arai1, Kazuwa Nakao1
1Department of Medicine and Clinical Science (A.Y., T.F., E.K., M.M., N.K., Y.K., H.A., K.N.), Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8507, Japan
2Fuji-Gotemba Research Laboratories (H.K., N.M.), Chugai Pharmaceutical Company, Limited, Gotemba, Shizuoka 412-8513, Japan

Tóm tắt

Skeletal dysplasias are a group of genetic disorders characterized by severe impairment of bone growth. Various forms of them add to produce a significant morbidity and mortality, yet no efficient drug therapy has been developed to date. We previously demonstrated that C-type natriuretic peptide (CNP), a member of the natriuretic peptide family, is a potent stimulator of endochondral bone growth. Furthermore, we exhibited that targeted overexpression of a CNP transgene in the growth plate rescued the impaired bone growth observed in a mouse model of achondroplasia (Ach), the most frequent form of human skeletal dysplasias, leading us to propose that CNP may prove to be an effective treatment for this disorder. In the present study, to elucidate whether or not the systemic administration of CNP is a novel drug therapy for skeletal dysplasias, we have investigated the effects of plasma CNP on impaired bone growth in Ach mice that specifically overexpress CNP in the liver under the control of human serum amyloid P component promoter or in those treated with a continuous CNP infusion system. Our results demonstrated that increased plasma CNP from the liver or by iv administration of synthetic CNP-22 rescued the impaired bone growth phenotype of Ach mice without significant adverse effects. These results indicate that treatment with systemic CNP is a potential therapeutic strategy for skeletal dysplasias, including Ach, in humans.

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Endocrinology

Tập 150 Số 7

3138-3144

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