Recombinant human epidermal growth factor(Kyung Hee University)

Bone regeneration depends on vascularization in the pertaining site. This study aims to investigate autogenous bone grafts mixed with recombinant human vascular endothelial growth factor (rhVEGF) effect on bone regeneration in rat mandibular bone defect.

Using 32 Wistar Albino rats, our experimental study consists of 4 groups: Group1 (control group), the defect was empty; Group 2, autogenous bone graft only; Group 3, gelatin sponge plus rhVEGF applications; Group 4, autogenous bone graft plus rhVEGF applications. The rats were sacrificed on the 28th day after the operation. New bone regeneration was analyzed histologically and immunohistochemically.

Our histological analyses revealed that new bone regeneration in Group 3 was enhanced in comparison to Group 1 and Group 2. However, autogenous bone grafts combined with rhVEGF provided the best outcome in conjunction with the increased remodeling of the new bone.

In the light of our results, it can be concluded that autogenous bone grafts in combination with rhVEGF can, potentially, enhance neovascularization and bone regeneration.

We studied the feasibility, safety, tolerability and pharmacokinetics of intracerebroventricular delivery of recombinant human vascular endothelial growth factor in patients with amyotrophic lateral sclerosis. In this phase I study in patients with amyotrophic lateral sclerosis, the study drug was delivered using an implantable programmable pump connected to a catheter inserted in the frontal horn of the lateral cerebral ventricle. A first cohort received open label vascular endothelial growth factor (0.2, 0.8 and 2 µg/day), a second cohort received placebo, 0.8 or 2 µg/day of study dug. After the 3-month study period, all patients could participate in an open label extension study. In total, 18 patients with amyotrophic lateral sclerosis, seen at the University Hospitals in Leuven were included. The surgical procedure was well tolerated in most patients. One patient had transient postoperative seizures, due to an ischemic lesion along the catheter tract. The first 3-month study period was completed by 15/18 patients. Administration of 2 µg/day vascular endothelial growth factor resulted in sustained detectable levels in cerebrospinal fluid. A pulmonary embolus occurred in 3 patients, in 1 patient in the first 3-month study, and in 2 patients during the open label extension study. The study drug was well tolerated in the other patients, for up to 6 years in the open label extension study. Our study shows that intracerebroventricular administration of 2 µg/day of vascular endothelial growth factor to patients with amyotrophic lateral sclerosis is feasible, results in detectable cerebrospinal fluid levels and is well tolerated in most patients. The most common serious adverse event was a pulmonary embolus.