Abstract 2194: A Novel Therapy Using Control-Released Basic Fibroblast Growth Factor in Patients with Peripheral Artery Disease: Comparison with Bone Marrow Mononuclear Cell Implantation
Objective: Basic fibroblast growth factor (b-FGF), a potent mitogen for endothelial cells with angiogenic property, is one of the key factors for angiogenesis which takes place by bone marrow mononuclear cell implantation (BMCI). We recently developed a b-FGF incorporating biodegradable hydrogel enabling b-FGF to be released at the site of action for 2–4 weeks (Tabata Y et al, J. Biomater. Sci. Polym. Ed. 1999). The aim of this study was to confirm safety and efficacy of the new protein therapy using control-released b-FGF in patients with peripheral artery disease in comparison with BMCI.
Methods: Limb ischemia was confirmed by digital subtraction angiography in all patients. After screening for preexisting coronary artery disease, stroke and malignancy, patients suffering (Fontaine class 3 or 4) from arteriosclerosis obliterans or Buerger’s disease were divided into b-FGF group (n=4, 64 ± 11 y/o) or BMCI group (n=7, 64 ± 14 y/o). Suspension of either gelatin hydrogel containing 600 μg of b-FGF or bone marrow mononuclear cells (0.4–5.1 x1010 in total) was administered into the calf and foot muscles of ischemic limbs. We evaluated visual analog pain scale, tissue blood flow by 99mTc-tetrofosmin scintigraphy, transcutaneous oxygen tension (TcPO2) and ankle-brachial index (ABI) before and 4 weeks after each treatment.
Results: Pain scale significantly decreased in both groups (b-FGF 64 ± 11 to 6 ± 6, P<0.01, BMCI 68 ± 42 to 5 ± 8 mm, P<0.01), which was supported by significant increase in TcPO2 (b-FGF 31 ± 15 to 57 ± 2.3, P<0.01, BMCI 8.3 ± 10 to 30 ± 21 mmHg, P<0.05). There was also a tendency to increase in tissue blood flow (b-FGF 0.5 ± 0.2 to 0.6 ± 0.2, NS, BMCI 0.7 ± 0.3 to 0.9 ± 0.2 count ratio/pixel, NS) and in ABI (b-FGF 0.7 ± 0.4 to 1.0 ± 0.2, NS, BMCI 0.5 ± 0.2 to 0.6 ± 0.1, NS), which did not reach statistically significance. Adverse events including limb amputation did not occur during the 4 weeks in both groups.
Conclusion: These findings suggest that control-released b-FGF therapy is as safe as BMCI, and its efficacy after 4 weeks appears to be comparable. Thus, this therapy may be able to become an alternative to BMCI.