Abstract
Great potential for limb salvaging with basic fibroblast growth factor (FGF-2) expressed from a Sendai virus vector with the full-length viral genome (SeV/FGF-2) in the target muscle was demonstrated in animal models of severe limb ischemia. The exogenously expressed FGF-2 induced other endogenous angiogenic factors, including vascular endothelial growth factor and hepatocyte growth factor in a highly concerted fashion, and this was shown to underlie the remarkable limb salvaging. These results led to the initiation of a phase I/IIa clinical trial for peripheral arterial disease (PAD) of humans. To be better prepared for unforeseen adverse events, this clinical trial used the F gene-deleted, nontransmissible, and hence safer (than SeV/FGF-2) version that carried the human FGF-2 gene (∆FSeV/FGF-2; product code, DVC1-0101). Overall, DVC1-0101 appeared to be safe, giving rise to no serious adverse events in various criteria. Moreover, it exerted a significant therapeutic effect from a number of clinical aspects. DVC1-0101 represents the first case of the potential diverse medical applications of SeV vector. It is now hoped to move on to an advanced phase of clinical trial with a larger number of patients and placebo group to firmly establish the safety and efficacy of DVC1-0101.
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Acknowledgments
The authors thank Professor Yoichi Nakanishi, Mss. Keiko Kikutake, Michi Onizuka, and Nozomi Kataoka for their clinical research coordination, Ms. Akiko Kanaya for her help with drug preservation, Ms. Mio Yoneda-Maehara for her help with the trial paperwork, and Ms. Rio Yamauchi, Mr. Takeshi Maruoka, and Minoru Ido at EPS Co. for their help with the trial management. This study was supported in part by a Grant for Translational Research from MHLW to Y.Y.
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Yonemitsu, Y., Matsumoto, T., Maehara, Y. (2013). Gene Therapy for Peripheral Arterial Disease Using Sendai Virus Vector: From Preclinical Studies to the Phase I/IIa Clinical Trial. In: Nagai, Y. (eds) Sendai Virus Vector. Springer, Tokyo. https://doi.org/10.1007/978-4-431-54556-9_8
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DOI: https://doi.org/10.1007/978-4-431-54556-9_8
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