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

Background: The purpose of the present phase I clinical trial was to evaluate the safety, tolerability, and preliminary efficacy of naked DNA therapy expressing two isoforms of hepatocyte growth factor (pCK-HGF-X7) in critical limb ischemia (CLI) patients.

Materials And Methods: Twenty-one patients with CLI were consecutively assigned to receive increasing doses (cohort I: 4  mg; cohort II: 8  mg; cohort III: 12  mg; and cohort IV: 16  mg) of pCK-HGF-X7, which was administered into the ischemic calf and/or thigh muscle at days 1 and 15. A safety and tolerability evaluation and measurement of pain severity score using a visual analog scale (VAS), ulcer status, transcutaneous oxygen (TcPO(2) ) and ankle-brachial index (ABI) were performed throughout a 3-month follow-up period.

Enhanced cardioprotective effects by coexpression of two isoforms of hepatocyte growth factor from naked plasmid DNA in a rat ischemic heart disease model.

Background: The therapeutic potential of pCK-HGF-X7, a naked DNA designed to express two isoforms of hepatocyte growth factor (HGF(723) and HGF(728) ), was studied in the rat ischemic heart disease model.

Methods: First, the kinetics of gene expression was examined by injecting pCK-HGF-X7 DNA into the rat heart. Second, the cardioprotective effects were compared between the two naked DNA constructs, expressing a single (HGF(728) ) or both isoforms (HGF(728) and HGF(723) ) of HGF, in the rat ischemic heart disease model.

Human hepatocyte growth factor (VM202) gene therapy via transendocardial injection in a pig model of chronic myocardial ischemia.

Background: Hepatocyte growth factor (HGF) may stimulate angiogenesis. We examined the safety and therapeutic potential of the HGF plasmid (VM202) in pigs with chronic myocardial ischemia.

Methods And Results: We delivered VM202 or vehicle transendocardially to 4 groups of pigs: vehicle control (n = 9); high-dose VM202 (n = 9); low-dose VM202 (n = 3); and normal control (no ischemia; n = 1).

Therapeutic angiogenesis using naked DNA expressing two isoforms of the hepatocyte growth factor in a porcine acute myocardial infarction model.

Objective: We evaluated the potency of therapeutic angiogenesis using intramyocardial injection of naked DNA expressing two isoforms of hepatocyte growth factor (pCK-HGF-X7) in a porcine myocardial infarction model.

Methods: Four weeks after left anterior descending coronary artery ligation, 14 pigs were allocated to pCK-Null (negative control, n=7) or pCK-HGF-X7 (n=7) treatment groups. Gated myocardial single photon emission computed tomography was performed 4 and 8 weeks following coronary ligation.

Effects of IL-1beta on gene expression in human rheumatoid synovial fibroblasts.

IL-1 is one of the key mediators involved in the pathogenesis of rheumatoid arthritis (RA) and is known to affect the level of gene expression in various settings. We investigated the effects of IL-1beta on the expression of 240 genes in rheumatoid synovial fibroblasts (RSFs) using a cDNA microarray. Total RNAs were prepared from RSFs stimulated with IL-1beta and hybridized to the microarray.

Electrotransfer of human IL-1Ra into skeletal muscles reduces the incidence of murine collagen-induced arthritis.

Background: It has previously been demonstrated that high levels of gene expression in skeletal muscles can be achieved after direct in vivo electrotransfer of naked plasmid DNA. The purpose of this study is to examine the potential of in vivo electroporation of plasmid DNA encoding human IL-1Ra for the prevention of murine collagen-induced arthritis (CIA).

Methods: DBA/1 mice were injected in gastrocnemius muscles with plasmid DNA followed by in vivo electroporation.

Protection against collagen-induced arthritis by electrotransfer of an expression plasmid for the interleukin-4.

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease, leading to cartilage and bone destruction. We investigated whether the electrotransfer of IL-4 DNA could regulate the disease progress of murine collagen-induced arthritis (CIA). The maximum serum level of mIL-4 was measured by 340 pg/ml on day 1 following DNA transfer.

Angiostatin gene transfer as an effective treatment strategy in murine collagen-induced arthritis.

Objective: To determine the efficacy of local therapy with human angiostatin gene in murine collagen-induced arthritis (CIA).

Methods: DBA/1 mice were immunized with bovine type II collagen. Before the onset of arthritis, NIH3T3 fibroblasts, transduced with angiostatin-expressing retroviral vectors or control vectors, were transplanted into the knee cavity.