Gene Therapy to Treat Peripheral Artery Disease

Peripheral artery disease is a narrowing of blood vessels in the limbs, usually caused by the progression of atherosclerosis, and consequent failure to deliver enough oxygen to cells. Tissues fail to heal and grow, and ultimately die, causing serious medical conditions along the way. Here researchers are trying a more sophisticated form of patch therapy, not addressing the root causes, but altering the signals delivered to cells in order to create greater growth and regrowth in blood vessels. This has the potential to partially compensate for the progression of blood vessel narrowing, but like all compensatory approaches it can only buy a little time, not fix the problem:

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 critical limb ischemia (CLI), a severe form of peripheral artery disease. The HGF gene in VM202 produces two isoforms of HGF proteins that are naturally found in the human body. HGF is a growth factor that induces angiogenesis and acts as a neurotrophic factor. After VM202 is injected into a patient's muscle, it is taken up by a cell and produces the HGF proteins, which are then released from the cell and may induce new blood vessel formation by activating various signaling pathways. In this way, VM202 may provide clinical benefits to CLI patients.

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 2 weeks apart) in the muscle of the diseased leg. "We are looking forward to conducting a phase III trial to better understand the potential of this novel approach, especially in treating non-healing 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 (16 mg total) VM202 showed significantly better ulcer healing than did patients who were treated with placebo injections. In fact, 62% of ulcers treated with high-dose VM202 healed completely compared with only 11% of ulcers treated with placebo. Statistically meaningful results were also seen in tissue oxygenation (TcPO2 levels). Of patients treated with high-dose VM202, 71% showed increased TcPO2 levels, whereas only 33% of control patients showed better tissue oxygenation.