Modern methods of CVD treatment
This situation leads to the search for new methods of treatment for these diseases, and one of the most promising methods is therapeutic angiogenesis, which improves the blood supply to the affected heart tissue or limbs through the growth of new blood vessels.
Currently, there are three areas of research or treatment in this field: the use of recombinant proteins, cellular and gene therapy.
According to Nina Mzhavanadze, a member of the Department of Angiology, Vascular and Operational Surgery and Topographic Anatomy at the Pavlov Ryazan State Medical University, the main studies in the field of post-genomic technologies are devoted to recombinant proteins – growth factors VEGF 165, FGF 1, FGF 2, as well as hepatocyte growth factors.
Unfortunately, studies of the factors FGF1 and FGF 2 have not yielded the desired results, which, apparently, is associated with their rapid decomposition in the blood flow. Studies of VEGF proteins have also not yielded any significant positive effect, so additional studies are needed in this direction.
A more promising method of modern therapy is cellular technology for the induction of angiogenesis, and their use in the treatment of CHD appears to be the most effective. The main objects of research for clinical therapy are progenitor endothelial cells and multipotent mesenchymal stem cells, which are highly effective in creating proteins – growth factors.
The possibilities of adipose tissue stem cells capable of transforming into endothelial cells and producing several types of such proteins are being actively studied. Finally, a number of researchers develop methods of autogenic cell transplantation of single-nucleus bone marrow cells and blood.
In the early 2000s, scientists actively attempted to use skeletal muscle embryos, but the research was unsuccessful, and now this type of therapy is not used. But placental cells isolated from umbilical cord blood showed good results in the treatment of lower limb ischemia.
Clinical studies are currently underway on the efficacy and safety of this type of therapy. In addition, clinical trials of endometrial regenerative cells are being carried out to promote the revascularization of ischemic lower limb muscles.
However, the production of cellular therapies is a complex process and requires specific equipment, as the drugs are produced from the patient’s own point of origin, i.e. there are certain difficulties in obtaining sufficient material for clinical purposes. A significant number of cells also die quickly after transplantation.
Finally, there are a number of organizational and economic challenges. All of these factors hinder the introduction of cellular therapy into a wide range of clinical practice. Therefore, research in the area of gene therapy, which is capable of solving problems that are inaccessible to cellular technologies, is of great importance.
According to the employee of the Scientific Center of Cardiovascular Surgery named after V.I. Lomonosov. Olga Demidova, the research of the influence of gene technologies on the course of ischemic disease of the lower limbs was started in 1981, when the patient was first introduced a gene medicine.
Two years later, nine cases of gene therapy with good clinical results were described, with patients with II and . In Russia, such studies have been conducted for 13 years, and some of them were conducted at the Institute named after M.V. Lomonosov. Bakulev under the guidance of Academician Leo Bokeria.
At present, the Bakulev Center will distribute the results of 12-year studies of therapy with the inductor VEGF 165, which showed a high percentage of patient survival and limb safety in Kink patients.
According to Roman Deev, Director of Science at the Human Stem Cells Institute (HSCI), in 2011 Professor Elena Parfyonova and her co-authors presented the results of their clinical study conducted with the participation of 30 patients with chronic lower limb ischemia.
Patients were introduced to the design on the basis of plasmid DNA, including the coding part of the VEGF 165 gene with the working title “Corvian”. As a result of the experiment, the growth of collateral vessels and improvement of blood flow in the affected limb were observed in 50% of patients.
Academician of the Russian Academy of Sciences Nikolay Bochkov and specialists of the Russian Scientific Center of Surgery named after V.I. Lomonosov were also involved in the experiment. Alexander Gavrilenko and Dmitry Voronov of the Petrovsky Russian Research Center for Surgery have carried out a number of studies devoted to the study of viral genotherapeutic structures that carry the genes of VEGF and (or) ANG in the comprehensive treatment of patients with KINK.
In turn, the researchers of the Acad Center for Surgery. The researchers of the B.V. Petrovsky Center for Surgery have analyzed the effectiveness of genetically engineered complexes of angiogenesis stimulation on the basis of genes of endothelial growth factors, in which the results of 10-year observations were systematized.
As the vascular surgeon of the center Evgeny Oleinik told, such constructions appeared to be effective both in combination with operations and at conservative therapy. Moreover, the use of these designs has improved the long-term results. According to Oliinyk, the effects achieved have been preserved for ten years and more, while remaining safe for all groups of patients.
In 2013, the team of specialists from Kazan Medical University presented the results of a pilot clinical study on the use of complex plasmid structures carrying VEGF and bFGF genes for the treatment of chronic ischemia of the lower extremities.
According to the study, six months after the application of the two-cassette plasmid vector pBud-VEGF165-FGF2, the blood circulation rate in the lower extremities increased by an average of 19%.
Another widely studied group of genes is the inducers of FGF and HGF proteins. Phase II of the clinical trial of the drug based on HGF in patients with CDC showed positive results in 70% of cases.
The results of the latest clinical trials have not yet been published, but we can already conclude that FGF and HGF agents are more promising in the treatment of CHD, while the genes responsible for the synthesis of VEGF and SDF are more effective for HINC.
The first example of the completion of the entire cycle of preclinical and clinical trials was the work on the implementation of Neovasculgen developed by HSCI. According to Igor Plaksa, HSCI researcher, the active component of Neovasculgen is a plasmid containing the gene VEGF 165, which encodes the synthesis of protein – the growth factor of vascular endothelium.
In muscle cells, the plasmid expresses the gene of the endothelial growth factor, which, in turn, increases the concentration of the endogenous factor. The development of collateral vessels begins, and as a consequence, the improvement of blood circulation in the muscle.
According to Ilya Staroverov, Head of the EITI Surgery Department of the Yaroslavl Medical Academy, the cost of Neovasculgen is quite high, but the methods of genetic engineering are generally very expensive and such drugs should be oriented to state support. But considering that the alternative to treatment is only amputation of the patient’s limb, the economic advantage of using the drug is not in doubt.
Three quarters of patients treated at the Yaroslavl Regional Clinical Hospital have improved their limbs. A few patients failed to help, but this was due to the fact that patients were admitted for treatment already in the condition of the CDC, i.e. with pronounced gangrene.
It takes at least a month to show the effect of treatment, explained the surgeon, and in some cases gangrene has already spread so much that there was simply not enough time to resume blood flow.