Improved vaccine against type 1 diabetes
Scientists at the Pittsburgh Children's Hospital, working under the guidance of Doctors Massimo Trucco and Nick Giannoukakis, have improved the method of treating type 1 diabetes based on the "re-education" of the patient's immune system.
Normally, dendritic cells play the role of instructors in the immune system: they secrete key foreign proteins-antigens and present them to T-lymphocytes. In case of failures in the immune system, dendritic cells can incite T-lymphocytes against any of the cell types of their own body. This leads to the development of autoimmune diseases, including type 1 diabetes, in which the immune system destroys insulin-producing beta cells of the pancreas.
In previous studies, the authors used a more sophisticated method of reprogramming dendritic cells. They were isolated from the patient's blood using leukapheresis (about 20 million cells in 2-4 hours of the blood filtration procedure) and cultured in a medium containing DNA segments antisense to the genes of proteins that transmit information from dendritic cells to T-lymphocytes, as well as short amino acid sequences of the insulin molecule. After that, dendritic cells were injected into the lymph nodes of the patient located next to the pancreas. When such dendritic cells met with lymphocytes aimed at destroying beta cells, something like the erasure of the program occurred. A course of six vaccinations made it possible to completely stop the process of destruction of beta cells, and in the early stages of diabetes development – to restore the function of insulin synthesis.
The new approach is less invasive for the patient, easier to implement and, according to the results of animal experiments, more effective. Dendritic cells are reprogrammed directly in the body. In experiments on diabetic mice, researchers injected a suspension of microspheres carrying segments of antisense DNA under their skin in the immediate vicinity of the pancreas. The dendritic cells contained in the skin absorbed microspheres, and the nucleic acids released at the same time reprogrammed them in the same way as in the previous technique. Dendritic cells migrating to the pancreas suppressed the activity of the immune system directed against insulin-producing beta cells, and within a few weeks the ability to synthesize insulin was restored in animals, which led to a decrease in glucose levels.
Currently, researchers are conducting the first phase of clinical trials of vaccination against type 1 diabetes using the first technique, with the isolation of dendritic cells using leukapheresis. Interim test results indicate the safety and effectiveness of the method.
If this and subsequent phases of clinical trials are successful, the authors plan to conduct clinical trials of a microsphere-based vaccine together with the developer of PROMAXX microsphere technology, Baxter Healthcare Corporation. If successful, such vaccination can be used not only for the treatment of diabetes that has already been detected, but also for the prevention of the disease in children belonging to the risk group.
Portal "Eternal youth" www.vechnayamolodost.ru based on the materials of ScienceDaily
03.06.2008