Enzyme replacement therapy prevents loss of bone and fat mass in murine homocystinuria.

Autor: Majtan T; Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado., Park I; Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado., Bublil EM; Orphan Technologies Ltd., Rapperswil, Switzerland., Kraus JP; Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado.
Jazyk: angličtina
Zdroj: Human mutation [Hum Mutat] 2018 Feb; Vol. 39 (2), pp. 210-218. Date of Electronic Publication: 2017 Nov 13.
DOI: 10.1002/humu.23360
Abstrakt: Skeletal and connective tissue defects are the most striking symptoms in patients suffering from classical homocystinuria (HCU). Here, we determined body composition and bone mass in three mouse models of HCU and assessed whether a long-term administration of enzyme replacement therapy (ERT) corrected the phenotype. The mouse models of HCU were analyzed using dual-energy X-ray absorptiometry and the data were complemented by plasma biochemical profiles. Both the mouse model lacking CBS (KO) and the one expressing human CBS mutant transgene on a mouse CBS null background (I278T) showed marked bone loss and decreased weight mostly due to a lower fat content compared with negative controls. In contrast, the HO mouse expressing the human CBS WT transgene on a mouse CBS null background showed no such phenotype despite similar plasma biochemical profile to the KO and I278T mice. More importantly, administration of ERT rescued bone mass and changes in body composition in the KO mice treated since birth and reversed bone loss and improved fat content in the I278T mice injected after the development of clinical symptoms. Our study suggests that ERT for HCU may represent an effective way of preventing the skeletal problems in patients without a restricted dietary regime.
(© 2017 Wiley Periodicals, Inc.)
Databáze: MEDLINE
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