Gene Therapy May Lead to New Options for Untreatable Diseases

Treatment can cause new blood vessel formation by activating signaling pathways.

Gene therapy offers potential as a treatment option for patients with debilitating diseases that have minimal therapeutic options, according to a recent study.

Researchers evaluated VM202, a human hepatocyte growth factor (HGF) gene found in plasmid DNA, to study the safety and efficacy of this gene therapy.

The study, conducted at Texas Heart Institute and published in Gene Therapy, showed that patients treated with a high dose of VM202 (16 mg total) had ulcers that healed significantly better than patients in the placebo group.

Sixty-two percent of patients in the high dose group had ulcers that healed completely, while only 11% were healed with the placebo injection.

There were also results in tissue oxygenation (TcPO2) levels. About 71% of patients treated with a high dose of VM202 had an increase in TcPO2 levels. Only 33% of placebo patients had any improvement in their TcPO2 levels.

"These positive results are exciting, and VM202 shows great promise for treating patients with this debilitating disease who often have limited therapeutic options," said principal study investigator Emerson C. Perin, MD, PhD. "We are looking forward to conducting a phase 3 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."

Researchers believe that if VM202 is injected into a patient’s muscle, it will be taken by a cell and produce HGF proteins. These are then released from the cell, creating new blood vessel formation by activating signaling pathways. This could have some clinical benefits to critical limb ischemia (CLI) patients.

CLI is a form of peripheral artery disease (PAD), which is when the peripheral arteries narrow -- most commonly in the legs. If it is not managed it can progress to CLI, causing the blood flow in the arteries to become blocked by plaque buildup and advanced atherosclerosis.

With the decrease in blood flow to the limbs comes the decrease in oxygenation of the tissues, leading to chronic pain, ulcers, and gangrene. For extreme cases, amputation can be a last resort.

Manufacturer ViroMed was approved by the FDA to initiate a phase 3 study for chronic, non-healing, ischemic foot ulcers in diabetes patients with VM202-PAD, in addition to other biopharmaceuticals targeting currently untreatable diseases.