FGF2 producing B. longum

Critical Limb Ischemia (CLI) is a manifestation of the most advanced stage of peripheral arterial disease with a severe obstruction of the arteries which markedly reduces blood flow to the lower extremities, progresses to the point of severe pain, tissue loss and worsening claudication symptoms. The number of patients with CLI increases year by year, yet amputation is often the only option available for 20-30% of patients with CLI (120,000 amputations annually in the U.S., 5-year survival rate of less than 30%). Attempted therapeutic strategies include using various angiogenic growth factors to improve blood vessel growth to augment perfusion. For instance, therapies targeting FGFs, VEGFs or HGF have been under clinical evaluation. However only limited success in therapeutic angiogenesis in clinical trials have been reported.

FGF2 expression i-DPS is designed to produce FGF2 at hypoxic lesions of chronic limb ischemia to promote vascularization and improve blood flow. In the chronic limb ischemia model in mice, improved blood flow of ischemia leg was observed by i.v. administration of FGF2 producing B. longum, and repeated i.v. administration was possible without toxicity. Furthermore, B. longum colonies were only found in disease muscles but not in normal muscles, implying that our recombinant B. longum was selectively delivered to and amplified in hypoxic lesions without distributing in normal tissues. FGF2 producing i-DPS is a novel drug candidate against CLI and may help CLI patients avoide amputations and improve QOL.