A phase I clinical study of naked DNA expressing two isoforms of hepatocyte growth factor to treat patients with critical limb ischemia

Abstract

These results support the performance of a phase II randomized controlled trial with pCK-HGF-X7.

Phase 1/2 Open-label Dose-escalation Study of Plasmid DNA Expressing Two Isoforms of Hepatocyte Growth Factor in Patients With Painful Diabetic Peripheral Neuropathy

“…This result is consistent with the safety data from previous preclinical and clinical studies performed with the same investigational drug. [7][8][9][10][11][14][15][16] The complete lack of significant side effects with the highest (16 mg) dose in this study suggests that it may be possible to increase the dose safely in future studies.…”

“…[14][15][16] Encouraged by such results, we investigated in this phase I/II study the safety and tolerability of VM202 in patients with PDPN. The efficacy of VM202 in pain reduction and enhancement of quality of life was also preliminarily evaluated using several questionnaires for symptom assessment.…”

“…The safety and efficacy of VM202 for cardiovascular diseases have been demonstrated previously in extensive preclinical studies [7][8][9][10][11][12][13] as well as three independent phase I trials. [14][15][16] VM202 is a plasmid DNA containing a therapeutic gene, HGF-X7, which encodes two isoforms of hepatocyte growth factor (HGF). 7 HGF is a multifunctional, mesenchymederived cytokine with potent angiogenic and antifibrotic activities.…”

Biochemical and Biophysical Cues in Matrix Design for Chronic and Diabetic Wound Treatment

“…130 The safety of cDNA delivery using naked plasmids has been demonstrated in a number of recent clinical studies using intramuscular injections of hepatocyte growth factor (HGF) DNA plasmids to treat critical limb ischemia. [131][132][133][134] Importantly, local delivery of HGF plasmids did not cause peripheral edema and did not increase systemic HGF protein level. 132 Therapeutic benefits, including reduced pain, increased ankle-brachial index, and improved wound healing, were observed in these studies and some ischemic ulcers healed completely.…”

“…132 Therapeutic benefits, including reduced pain, increased ankle-brachial index, and improved wound healing, were observed in these studies and some ischemic ulcers healed completely. [131][132][133][134] cDNA transfection usually results in transient expression of exogenous genes; therefore, methods have been developed to prolong their expression. Kulkarni et al encapsulated lipoplexes carrying eNOS encoding gene in fibrin microspheres and formed a ''fibrin in fibrin'' temporal release system.…”