Updated on 1 August 2012
The third target disease of VM202 is coronary artery disease (CAD), which ranks as the number one or number two cause of death in developed countries. CAD includes various heart-related diseases, such as myocardial infarction and angina pectoris.
As CAD is mainly caused by atherosclerosis, which is a degenerative process, patients with CAD may be asymptomatic for years. However, as it progresses, ischemic conditions worsen, due to continued plaque deposition. As a consequence, vessel occlusion, loss of arterial elasticity, and increased stenosis decrease coronary blood flow, resulting in an oxygen deficiency in the heart. Angina pectoris is the most common clinical manifestation of these chronic ischemic conditions. When angina is predictably induced by physical exertion, it is termed stable exertional angina. Untreated, stable angina can progress to various acute coronary syndromes, including unstable angina, myocardial infarction, heart failure and sudden cardiac death. Regardless of the seriousness of this disease, current treatment options are limited to percutaneous coronary intervention (PCI) and coronary artery bypass graft surgery (CABG). In the US alone, CAD is responsible for over one million deaths and direct medical expenses of about $87.6 billion annually.
For all the three diseases (DPN, CLI, and CAD) that VM202 is targeting, current treatment methods have clear limitations, and there has been a strong need for development of improved therapeutic agents. A number of major pharmaceutical companies around the world have been trying to develop drugs and technologies to effectively cope with these diseases, but with very limited success. Amid Goliaths' unsuccessful struggles for an innovative drug for these diseases, a small biotech company named ViroMed stands out with their DNA-medicine VM202.
When VM202 is delivered to the affected area by a single intramuscular injection, this drug enters a small portion of the surrounding muscle cells. These cells then simultaneously produce the two isoforms of HGF proteins, which are subsequently secreted and bound to the cellular receptor called c-Met present on the surface of neighboring endothelial, smooth muscle, or neuronal cells. This interaction activates the c-Met pathway, triggering a series of biological reactions, including angiogenesis and prevention of cardiac remodeling. In the case of both CLI and CAD, the development of new blood vessels around the occluded arteries would improve blood flow to the affected areas. This would lead to increased perfusion and wound healing. In the case of PDPN, microvasculature will be restored, and this would allow the supply of much needed oxygen and nutrients to the nerve cells and the removal of toxic metabolites, thereby aiding in survival of the nerves.
HGF can also function as a neurotrophic factor. Sympathetic neurons express both HGF and its cognate receptor. When VM202 is injected along sural, peroneal, and saphenous nerves and their branches, the localized production of HGF, resulting from VM202 injection, promotes the growth of sympathetic neurons as well as axonal growth and regeneration.
Data from human trials