Two successful strategies for the prevention and treatment of craniosynostosis -- premature fusion of the sutures in the skull -- are reported online in Nature Genetics. At least one of the approaches may be testable in humans in the near term. Craniosynostosis is caused by the sutures of the skull closing too early in infancy, which affects normal brain and skull growth. It occurs in approximately 1 of every 2,500 live births. Apert syndrome, a rare but quite severe form of craniosynostosis, is caused in most cases by a specific mutation in a cell-surface receptor called FGFR2.
Chu-Xia Deng and colleagues created a mouse model of Apert syndrome that bears one of the most common FGFR2 mutations seen in humans. When these mice were crossed with mice expressing a 'short hairpin' RNA molecule specifically designed to block expression of the mutant form of FGFR2, the offspring that carry the FGFR2 mutation developed normally. The authors also report the involvement in the disease of an enzyme called ERK, which is regulated by FGFR2. When they injected a drug that inhibits ERK activity into pregnant mice carrying the FGFR2 mutation, the offspring showed no signs of Apert syndrome. Moreover, when the drug was injected at the onset of the disease during the early postnatal period, at least some of the treated mice maintained a normal appearance, although the treatment's effectiveness was greater in male than in female mice.
Drugs similar to those used in this study are already being tested in clinical trials as anticancer drugs, and may now have additional applications in the prevention and treatment of birth defects such as craniosynostosis.
Chu-Xia Deng (National Institutes of Health, Bethesda, MD, USA)
Abstract available online.
(C) Nature Genetics press release.
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