VM202 is a Safe, Beneficial Treatment for Limb Ischemia


The Korean biotechnology company ViroMed Co., Ltd. has announced the publication of a Phase 2 study that evaluated their VM202 product in patients with critical limb ischemia. This study involved 52 patients in the United States and showed that VM202 is not only safe, but also produced significant clinical benefits.

VM202 is a plasmid (small circle of DNA) that encodes the human hepatic growth factor (HGF) gene. When injected into muscles, VM202 is readily taken up by nearby cells that then quickly synthesize the two isoforms of HGF. Heightened HGF concentrations can treat ischemic cardiovascular diseases by inducing the formation of new blood vessels (angiogenesis). These new collateral vessels increase blood flow and tissue perfusion in the sick tissue, which effectively treats any tissue ischemia.

VM202

Severe obstruction of the arteries that feed the extremities (hands, feet and legs) is the cause of critical limb ischemia (CLI). The term “ischemia” refers to the starvation of a tissue for oxygen. The lack of sufficient blood flow to an organ or tissue can cause severe pain and even skin ulcers, sores, or gangrene. CLI-induced pain can awaken the patient during the night, and, therefore, is called “rest pain.” Rest pains often occur in the leg and is usually temporarily relieved by dangling the leg over the bed or getting up and walking.

CLI does not improve on its own. It is a severe condition that requires immediate by a vascular surgeon or vascular specialist.

Look at the right side of these angiograms and you will see that a vessel is obstructed and blood is not flowing through it. This is an example of Critical Limb Ischemia.
Look at the right side of these angiograms and you will see that a vessel is obstructed and blood is not flowing through it. This is an example of Critical Limb Ischemia.

In this Phase 2 study, patients were divided into three groups, one of which received a placebo treatment, the second of which received a low-dose treatment VM202, and a third group that received a high-dose of VM202.

Both patient groups that received VM202 showed improvement compared to the placebo group, but patients in the higher-dose group showed significantly better ulcer healing and higher tissue oxygen levels than the placebo group. For example, 62 percent of the ulcers healed in patients treated with high-dose VM202 compared to only 11 percent of ulcers in patients who were treated with the placebo. Also, 71 percent of patients who received the high-dose VM202 showed improved oxygen concentrations in their tissues, compared to only 33 percent of patients who were treated with the placebo.

Emerson C. Perin, Director of the Stem Cell Center at the Texas Heart Institute and the principal investigator of this Phase 2 study, said: “These positive results are exciting, and VM202 shows great promise for treating patients with this debilitating disease who often have limited therapeutic options. 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.”

ViroMed has already been granted an IND or Investigational New Drug approval by the USFDA to initiate a Phase 3 study in diabetic patients who suffer from non-chronic ischemic foot ulcers. This study will enroll 300 subjects who will be divided into a VM202 group and a placebo group. The treatment regiment will mimic that of this smaller Phase 2 study and will only follow patients for seven months. This time, ViroMed is interested in determining if VM202 helps wound closure, which will constitute the primary efficacy endpoint on this new study.

Godspeed ViroMed!!

Growth Factors to Heal the Heart


When the heart suffers a heart attack, local areas of the heart experience cell death as a result of blockage in a coronary vessel. The cell death is followed by local inflammation which causes further cell death and produces a heart scar. This produces a situation in which a portion of the heart does not contract and also does not conduct impulses to beat. Can this dead heart tissue live again?

Several experiments have used stem cells to refurbish the dead heart tissue, and a variety of different stem cells can clearly produce new heart cells that help the heart beat better. Can growth factors that stimulate cell growth and division do a similar job?

Just injecting growth factors into the bloodstream will not do because the growth factors will not spend any appreciable time in or around the heart cells. Is there another way to do it? Yes. The answer is hydrogels.

Hydrogels are semi-solid materials that can be made and in which the growth factors can be embedded. The hydrogels are gradually degraded while they release growth factors into the heart tissue. The slow but stead release of various growth factors can induce the heart to heal itself.

Works from the laboratory of Michael E. Davis at Georgia Institute of Technology and Emory University School of Medicine in Atlanta, Georgia have published a paper in PLoS ONE describing this very strategy. Using rats that had suffered heart attacks, Davis and his group applied a polyethylene glycol-based hydrogel laced with two growth factors, hepatic growth factor (HGF) and vascular endothelial growth factor (VEGF) to the hearts of these animals.

There were no immediate effects to the application of these hydrogels as determined by electrocardiograms. However, with the passage of time, some remarkable changes to the hearts of these rats were observed. Three weeks after the application of hydrogels to rat hearts, animals treated hydrogel material only, injected with growth factors only showed no significant improvement over those rats that were not injected with anything. But those rats whose hearts had been injected with hydrogels laced with VEGF showed a 50% increase in blood vessel density and those injected with hydrogel imbued with HGF and VEGF showed a 100% increase in blood vessel density. These same rats also showed a huge reduction in the size of the heart scar (41.5 % vs 13.9% fibrosis), and also showed significant increased in heart function after three weeks.

Why did these growth factors work so well? Several experiments conducted by Davis’ group showed that the stem cell population in the heart, the cardiac progenitor cells or CPCs, were pitched into overdrive by the growth factors, In short, in the presence of these two growth factors, the cells went nuts. They went to area where the hydrogel had been applied and made new heart muscle cells and blood vessels.

Therefore, these two growth factors can be applied to the heart to elicit healing within the heart after a heart attack. The hydrogels keep the growth factors there and release them slowly so tat they can perform their healing magic.

Hopefully this experiment will lead to preclinical studies in larger animals (pigs and sheep), and then, hopefully, clinical trials in human patients.  See Salimath AS, et al., PLoS ONE 2012 7(11) e50980.