Viruses will save you from diabetes
Type 1 diabetes is a chronic disease in which the body's immune system destroys its own beta cells of the pancreas that produce insulin, which leads to an increase in blood glucose levels.
One of the main goals of type 1 diabetes treatment is to preserve and restore functioning beta cells of the pancreas. This would lead to normalization of insulin secretion. But in patients with type 1 diabetes mellitus, replacement therapy in the form of the introduction of beta cells is probably doomed to failure, because new cells suffer and die from the same immune mechanisms that destroy their own cells.
Researchers from the University of Pittsburgh School of Medicine used adenoassociated viral vectors (AAV vectors) to deliver Pdx1 and MafA proteins to the pancreas, which reprogrammed alpha cells of the pancreas into insulin-producing beta cells.
Reprogramming alpha cells into beta-like ones carries great potential. This is due to the fact that as a result, other cells that are not susceptible to attack by the immune system will begin to produce insulin. This means that the result will be preserved for a long time.
To study the possibility of such treatment, researchers led by George Gittes used a method of gene therapy using viral vectors – specially modified viruses (in this case, adenoviruses) that are able to deliver the necessary proteins to target cells.
Pdx1 and MafA proteins, interacting with alpha cells of the pancreas, triggered the process of acquiring the functions of beta cells. As a result, beta-like cells are obtained, which are able to completely replace the functions of damaged beta cells. Alpha cells in this case are an ideal replacement, since they have morphological similarities with beta cells, are located in the pancreas, and there are quite a lot of them. The researchers compared "true" beta cells with beta-like ones obtained by reprogramming alpha cells. Almost complete similarity has been confirmed. As a result, the mice normalized blood glucose levels for a long time (on average for 4 months).
In a study on the culture of reprogrammed human alpha cells, the same persistent results were obtained.
Both images show human pancreatic cells treated with a drug to destroy insulin-producing beta cells. The photo on the left shows the result of the introduction of empty AAV vectors, on the right – AAV vectors with proteins reprogramming alpha cells. The green spots on the right photo are cells containing insulin.
Viral gene therapy using the AAV vector is currently being intensively researched for the treatment of other diseases.
Viral vectors are able to deliver proteins directly to the pancreas, this requires regular minimally invasive endoscopic intervention. However, there is a risk of inflammation of the pancreas in response to the procedure itself. In addition, the treatment process does not require immunosuppression (suppression of immune reactions), so there is a risk of adverse reactions in the form of inflammation in response to possible infection.
The biggest problem with this method of treatment is that in a study on mice, it was not possible to obtain a lasting lifelong effect: after some time, diabetes developed again in mice. Although translated into "human" time, the 4 months during which the effect of therapy in mice lasted are several years.
This study, in fact, is the first description of a clinically important, simple and isolated intervention in the autoimmune process in type 1 diabetes mellitus, which leads to normalization of blood glucose levels.
Given the impressive results obtained in the mouse study, it can be assumed that further clinical studies of AAV-vector gene therapy in patients suffering from type 1 or type 2 diabetes will be conducted in the very near future.
Currently, a group of researchers is planning to conduct a study of the developed treatment method on primates.
Article by Xiangwei Xiao et al. Endogenous Reprogramming of Alpha Cells into Beta Cells, Induced by Viral Gene Therapy, Reverses Autoimmune Diabetes is published in the journal Cell Stem Cell.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on EurikAlert: Gene therapy restores normal blood glucose levels in mice with type 1 diabetes.