Table 1.
Molecular and pharmacological in vitro and in vivo treatment modalities
| Model | Condition | Target | Treatment | Effects | Reference |
|---|---|---|---|---|---|
| In vitro cells calvaria animal, WT CD1 mice and rats | Wildtype | FGFR1 | Dominant negative Fgfr1 | Prevented fusion of the posterior frontal suture | Greenwald et al., 2001 |
| In vitro cells calvaria animal, Fgfr2C342Y/þ mouse | Crouzon syndrome | FGFR2 | FGFR tyrosine kinase inhibitor (PLX052) | Prevented premature fusion of the coronal suture | Eswarakumar et al., 2006 |
| In vitro cells calvaria animal, Fgfr2C342Y/þ mouse | Crouzon syndrome | FGFR2 | FGFR tyrosine kinase inhibitor (PD173074) | Prevented premature fusion of the coronal suture | Perlyn et al., 2006 |
| In vitro cells calvaria animal, Fgfr2P253R/þ mouse | Apert syndrome | ERK1/2 | MEK1 inhibitor (PD98059) | Partially prevented premature fusion of the coronal suture | Yin et al., 2008 |
| In vitro cells calvaria animal, Fgfr2S252W mouse | Apert syndrome | FGFR2 | Purified soluble form of FGFR2 (sFGFR2S252W) on nanogel vehicle | Prevented premature fusion of the coronal suture | Yokota et al., 2014 |
| In vivo-animal mouse model with Crouzon syndrome (Fgfr2C342Y/þ) and additional juxtamembrane mutations | Crouzon syndrome | FRS2A docking protein-dependent FGFR2C | Insertion of additional L424A and R426A mutations in mouse model with Crouzon syndrome (Fgfr2C342Y/þ) prevents recruitment and tyrosine phosphorylation of Frs2a | Prevented premature fusion of the coronal suture | Eswarakumar et al., 2006 |
| In vivo animal mouse model with Apert syndrome (Fgfr2S252W/þ) | Apert | ERK1/2 | Intraperitoneal injection of MEK1/2 inhibitor (U0126) | Prevented premature fusion of the coronal suture and partially rescued phenotype in Apert mouse | Shukla et al., 2007 |
| In vivo animal mouse model with Apert syndrome (Fgfr2S252W/þ) | Apert syndrome | FGFR2 | Heterozygous U6-Fgfr2S252W shRNA transgenic mouse mated with Apert syndrome mouse | Prevented premature fusion of the coronal suture and total rescue of phenotype in Apert mouse | Shukla et al., 2007 |
| In vivo animal mouse model with Beare-Stevenson cutis gyrata syndrome (Fgfr2+/Y394C) | Beare-Stevenson c utis gyrate syndrome | p38 | Intraperitoneal injection of p38 inhibitor (SB203580) | Amelioration of skin abnormalities, no effect on craniofacial phenotype | Wang et al., 2012 |
| In vivo animal rabbit model with bilateral coronal suture craniosynostosis | Bi-coronal craniosynostosis | TGFß2 | Neutralizing TGFß2 antibody after suturectomy | Prevented postoperative resynostosis of the coronal suture and improved intracranial volume and cranial vault growth | Mooney et al., 2007a, b Frazier et al., 2008 |
| In vivo animal chimeric human/nude (athymic) rat xenotransplant model of craniosynostosis containing Crouzon and Apert FGFR2 mutant human osteoblasts | Apert syndrome Crouzon syndrome | Noggm | rh Noggin | Prevented premature fusion of the coronal suture | Shen et al., 2009 |
| In vivo animal mouse model with postoperative resynostosis treated with suturectomy | Bi-coronal craniosynostosis | Noggm | Cells expressing Noggin | Inhibited bone formation | Cooper et al., 2009 |
rh, recombinant human; WT, wild type.