Improved quality of life in patients with no-option critical limb ischemia undergoing gene therapy with DVC1-0101.

Takuya Matsumoto,Keiji Yoshiya,Ryosuke Yoshiga,Yoshihiko Maehara,Michiko Tanaka,Yutaka Matsubara,Kumi Horiuchi-Yoshida,Yoshikazu Yonemitsu

doi:10.1038/srep30035

Abstract

Critical limb ischemia (CLI) has a poor prognosis and adversely affects patients’ quality of life (QOL). Therapeutic angiogenesis may improve mobility, mortality, and QOL in CLI patients. However, the effectiveness of gene therapy on such patients’ QOL is unknown. DVC1-0101, a non-transmissible recombinant Sendai virus vector expressing human fibroblast growth factor-2 gene, demonstrated safety and efficacy in a phase I/II study of CLI patients. We investigated the effects of DVC1-0101 on QOL in this cohort. QOL was assessed using the Short Form-36 health survey version 2 (SF-36) in 12 patients at pre-administration, 28 days, and 3, 6, and 12 months post-treatment. We examined differences between pre and post-administration QOL scores and correlations between QOL scores and vascular parameters. Patients demonstrated low baselines scores on every SF-36 dimension. Post-treatment scores showed significant improvements in physical functioning at 3 and 6 months (P < 0.05), role-physical at 3, 6, and 12 months (P < 0.05), bodily pain at 1, 3, 6, and 12 months (P < 0.05), vitality at 1, 6, and 12 months (P < 0.05), and physical component summary at 6 and 12 months (P < 0.05). DVC1-0101-based gene therapy may improve QOL in CLI patients over a 6-month period.

Highlights

Gene therapy clinical trial in critical limb ischemia (CLI) patients who were ineligible for standard vascular interventions (‘no-option’ CLI) completed in March 201113
The current study investigated the effects of gene therapy using DVC1-0101 on quality of life (QOL) measures in 12 patients with CLI, initially treated in the above study[13]
FGF-2 was the first angiogenic factor shown to improve walking performance in Peripheral arterial disease (PAD) patients[15] and Sendai virus-expressed FGF-2 demonstrated excellent limb-salvaging effects compared with other factors and vectors[11,12]

Summary

Introduction

Gene therapy clinical trial in CLI patients who were ineligible for standard vascular interventions (‘no-option’ CLI) completed in March 201113. CLI patients experience significant limitations in terms of their physical functioning and functional status, improving their QOL, as well as their clinical status, has become a vital treatment goal in these patients[14]. Innovative gene therapy is still in the early clinical trial phase, and QOL data are lacking. The current study investigated the effects of gene therapy using DVC1-0101 on QOL measures in 12 patients with CLI, initially treated in the above study[13]

Methods

Results

Conclusion