Anti-TGF-??2 Antibody Therapy Inhibits Postoperative Resynostosis in Craniosynostotic Rabbits

Abstract

These data support the initial hypothesis that interference with TGF-beta2 function inhibited postoperative resynostosis in this rabbit model. They also suggest that this biologically based therapy may be a potential surgical adjunct to retard postoperative resynostosis in infants with craniosynostosis.

Comparison of Craniofacial Phenotype in Craniosynostotic Rabbits Treated with Anti–Tgf-β2 at Suturectomy Site

“…Suturectomy control rabbits were somewhat smaller than IgG control individuals for most distances of the snout and face (by 3% to 4%), despite being slightly longer in a distance of the neurocranium, whereas anti-Tgf-β2 rabbits were somewhat larger than IgG control rabbits in most distances (up to 4.8%). Mooney et al (2007a) reported similar findings in that IgG control rabbits exhibited slightly slower reossification rates than did suturectomy control rabbits at 25 and 42 days of age, although the differences were not statistically significant. The authors suggested that this was probably not an effect of the IgG but rather was due to the presence of the collagen vehicle itself in the suturectomy site, which may have had an osteoinhibitory effect on reossification of the suturectomy site during degradation (Mooney et al, 2007a).…”

“…Mooney et al (2007a) reported similar findings in that IgG control rabbits exhibited slightly slower reossification rates than did suturectomy control rabbits at 25 and 42 days of age, although the differences were not statistically significant. The authors suggested that this was probably not an effect of the IgG but rather was due to the presence of the collagen vehicle itself in the suturectomy site, which may have had an osteoinhibitory effect on reossification of the suturectomy site during degradation (Mooney et al, 2007a). A recent in vitro study (Premaraj et al, 2006) also has shown that the collagen vehicle alone had a short-term inhibitory effect on osteoblast cell number in culture.…”

“…In considering the findings of this study, it should be noted that resynostosis was still seen in the anti-Tgf-β2 antibody treatment group before the end of the rabbit neurocranial growth phase (~84 days of age) (Mooney et al, 2007a(Mooney et al, , 2007b. This could indicate that antibody therapy delivered via a resorbable collagen vehicle may have only a transitory effect and alternative methods will have to be explored for prolonged delivery of such biological therapies (Warren et al, 2003;Mooney et al, 2004).…”

“…A recent in vitro study (Premaraj et al, 2006) also has shown that the collagen vehicle alone had a short-term inhibitory effect on osteoblast cell number in culture. Because the ultimate goal of this research is to inhibit postoperative resynostosis and to improve craniofacial growth, this should not be viewed as a confounding variable, although future studies designed to facilitate osteogenesis using various growth factors delivered by this collagen vehicle should take this into consideration (Mooney et al, ,2007a(Mooney et al, ,2007bPremaraj et al, 2006). Ideally, the effects of collagen alone should be compared experimentally with treatment with collagen plus Tgf-β2 inhibition to delineate more clearly the contribution of each material to bone growth.…”

“…Using the same rabbit colony, Mooney et al (2007a) demonstrated that anti-Tgf-β2 treatment delays postoperative resynostosis of the coronal suture. They also showed that, as expected, more cranial growth occurs in the anteroposterior (A-P) direction, and intracranial volume is significantly higher by 84 days of age than without antibody treatment (Mooney et al, 2007b).…”