The research team of the Kazan State Medical University leaded by M.O. Mavlikeev and M.V. Plotnikov has shown that Neovasсulgen treatment for patients with lower limb ischemia increases amount of blood vessels in skeletal muscle.
The results of morphological study of were published in Russian scientific journal «Genes and Cells».
In Russia every year lower limb ischemia leads to 35 thousand amputations, and many of patients are of working age. Most of therapeutic methods aim to save a limb, but their effectiveness is poor. The development of collateral circulation very important for these patients.
Neovasculgen® is the first-in-class gene-therapy drug developed by Human Stem Cells Institute for treatment of Peripheral Arterial Disease (PAD), including Critical Limb Ischemia (CLI), caused by atherosclerosis with therapeutic angiogenesis mechanism of action.
The drug is a circular DNA (plasmid), containing human gene VEGF 165 (VEGF — Vascular Endothelial Growth Factor), that stimulates the growth of collateral blood vessels (аngiogenesis). Neovasculgen® received marketing authorization in 2011, and in 2012 was launched in the Russian market.
The program of pre-clinical studies for each drug always includes morphological studies in animals. When the readings allow such research is carried out on volunteers. Vessels grown in the ischemic muscle in humans after Neovasculgen treatment have not previously been visualized by direct methods, only with radiological or scintigraphic methods. This was due to the fact that doctors were afraid of a risk that wounds after a biopsy will not be healed due to the lack of circulation. However, the use of VEGF 165 gene inducer has reduced the risk significantly and such study has become possible.
6 patients took part in the published study. A biopsy of the gastrocnemius muscle of patients together with the measurement of hemodynamic parameters was conducted prior to drug administration and 3 months after. Biopsies were examined histologically and immunohistochemically, doctors assessed the ratio of connective and muscular tissue, the number of capillaries, the degree of cell proliferation (growth) in the tissues.
It has been found that the tissue of patients respond to gene therapy in various ways. In patients who initially had high density of capillaries and a small amount of connective tissue three months after the treatment increased muscle fiber size and number of proliferating cells were observed.This was interpreted as improvement in muscle regeneration in response to hypoxic damage experienced by patients with ischemia and hence production of endothelial growth factor (VEGF165) resulted in effects not directly related to the growth vessel. In patients with initially reduced amount of capillaries and large amount of connective tissue Neovasculgen therapy resulted in increase of capillary network density, reduction of fibrosis and increase in muscle size. Level of proliferating cells did not differ from the initial. In this case, VEGF165 induced growth of endothelium and collateral vessels.
According to the researchers, the results are another evidence for the feasibility of pro-angiogenic therapy in a second group of patients.
At the end of December 2014 the Russian Strategic Initiatives Agency’s advisory council endorsed HSCI’s program called «The development of the production and promotion of innovative drug Neovasculgen». RSIA will accompany the project and support the inclusion of Neovasculgen in the list of Vital and Essensial Drugs (VED).
Therapeutic angiogenesis has great potential, and Neovasculgen drug can be used for the treatment of a number of other ischemic conditions. Right now Human Stem Cell Institute is working to expand the indications for use of the drug. The company plans to obtain data on the clinical efficacy in the treatment of coronary heart disease (CHD) in the treatment of diabetic foot syndrome and traumatic injuries of peripheral nerves.
