Gene therapy against lower limb ischemia
The main diseases leading to ischemia of the lower extremities are atherosclerosis, thrombangiitis and endarteritis (inflammation of the arteries), diabetic vascular lesion or diabetic angiopathy, obliterating atherosclerosis, trauma.
The most severe and difficult to treat are inflammatory and diabetic lesions. Blockage or narrowing of the vessel, which occurs in these diseases, leads to the development of chronic arterial insufficiency. At first, the body compensates for the obstruction of the main vessels by the development of small detours, but when walking, such a patient feels the need for periodic stops. As the vascular lesions progress, compensation is disrupted and critical ischemia develops, followed by gangrene.
An experienced doctor can diagnose a patient with critical ischemia from a distance. As a rule, a sick person sits with his leg down, constantly rubbing it. The face takes on a pained look. It is almost impossible to make the patient lie on the bed for an hour, he will still lower his leg. The stagnation of venous blood in the lowered limb increases the degree of oxygen transfer from the blood to the tissues and reduces pain. However, the resulting edema compresses the already poorly filled arterial vessels and further worsens blood circulation, leading to the appearance of areas of dead skin and tissues, the formation of non-healing ulcers. Due to lack of oxygen and nutrition, sensitive nerves become inflamed and unbearable burning pain occurs. All measures aimed at pain relief bring only temporary relief.
Despite the significant success of microsurgical methods of restoring arterial patency, in most severe cases of lower limb ischemia, patients are offered high amputations, since no treatment methods can relieve pain and gangrene progression.
For more than 20 years, scientists have been developing alternative therapeutic methods for the treatment of lower limb ischemia. Gene therapy drugs, which are based on the principle of influencing the disease with the help of genes transferred to the cells of the patient's body, are now considered one of the most promising areas in this field. The concept of restoring the vascular bed with the help of gene therapy drugs began to develop especially actively after scientists discovered the so-called vascular endothelial growth factor (VEGF).
The first clinical studies of gene therapy for the treatment of cardiovascular diseases began in the late 1990s. To date, the safety of using such therapy has been confirmed by substantial evidence. For 20 years, studies have been conducted on more than 1,000 patients, and at the moment no undesirable side effects have been reported (according to the American Heart Association, 2009).
In 1996, The Lancet published the first report on the use of plasmid vascular growth factor VEGF165 for the treatment of peripheral artery disease, which showed the safety of the technique, as well as the improvement of hemodynamic parameters in patients and accelerated healing of trophic ulcers.
Subsequently, studies of plasmid VEGF165 were conducted on patients with diabetic angiopathy and critical limb ischemia. It was noted that in comparison with the control groups, patients of the VEGF165 group were significantly less likely to undergo amputations, more cases of healing of skin ulcers were noted, and a greater degree of improvement in hemodynamic parameters was also observed.
As populations in developed countries age, the number of patients with intermittent lameness and critical limb ischemia increases. It is necessary to actively develop methods of using gene therapy and other non-traditional treatment approaches to alleviate the burden of ischemic disease and improve the quality of life of this continuously growing group of patients.
In July 2009, the Russian biotechnological company, JSC "Human Stem Cell Institute" received official permission from Roszdravnadzor of the Russian Federation to conduct clinical trials of the first Russian gene therapy drug with the VEGF165 gene for the treatment of chronic lower limb ischemia.
Phase I and IIa clinical trials were completed in February 2010, and in April 2010, permission was obtained to conduct phase IIb/III clinical trials of this drug.
Portal "Eternal youth" http://vechnayamolodost.ru according to the materials of the press service of JSC "ISKCH"
06.09.2010