A clinical study published in the January issue of Gene Therapy reports the results of a DNA-based gene therapy that may offer a therapeutic option for critical limb ischemia (CLI) in those without other options. The study examined the safety and efficacy of gene therapy with a plasmid DNA containing human hepatocyte growth factor (HGF) gene, called VM202, in 52 patients with CLI at 16 hospitals and research centers in the United States and Korea. VM202 was found to be safe and well tolerated and showed clinical benefits in CLI patients who had no other treatment options. Both ulcer healing and tissue oxygenation improved significantly in patients who were given four series of VM202 injections (spaced two weeks apart) in the diseased leg’s muscle.
CLI is a serious form of peripheral artery disease (PAD), a cardiovascular disease caused by narrowing of the peripheral arteries, most commonly in the legs. If not managed properly in the early stages, PAD can progress to CLI where the blood flow in the arteries becomes severely obstructed or blocked by plaque buildup and advanced atherosclerosis. This restricted blood flow reduces oxygenation of the tissues, which leads to chronic pain, ulcer formation, and possibly gangrene. As the tissue dies, amputation can become a last resort in extreme cases of CLI.
Emerson C. Perin, MD, PhD, director of the Stem Cell Center at the Texas Heart Institute (THI) and the principal investigator of the study, said, “We are looking forward to conducting a phase III trial to better understand the potential of this novel approach, especially in treating nonhealing ulcers, which is a serious symptom that often leads to amputation because of the lack of medical therapies available.”
In the study, patients treated with high-dose (16mg total) VM202 showed significantly better ulcer healing than did patients who were treated with placebo injections. In fact, 62 percent of ulcers treated with high-dose VM202 healed completely compared with only 11 percent of ulcers treated with placebo. Statistically meaningful results were also seen in tissue oxygenation (TcPO2 levels). Of patients treated with high-dose VM202, 71 percent showed increased TcPO2 levels, whereas only 33 percent of control patients showed better tissue oxygenation.
This articles was adapted from information provided by THI.