The Blog of Science

Recent research carried out by Lawrence Chan and coworkers at Baylor College of Medicine brings new hopes in the battle against diabetes, this time through gene therapy procedures done on mice.

What is gene therapy?

The idea about gene therapy consists of ‘repairing’ malfunctioning cells by introducing a gene or genes into them. In the case of diabetes, scientists seek to enable insulin production in patients that lost the ability to make insulin on their own. However, after many years of gene therapy research, scientists knew that just inserting the gene for insulin into the patients’ DNA would not work. The cells acquiring the gene produce insulin all right, but insulin synthesis needs to be tightly controlled and that is a very complex process that can not be achieved by means of gene therapy.

The idea underlying Dr Chan’s work is to induce cells in the liver to become alike pancreas cells to a limited extent, but enough to produce insulin in a properly controlled way.

Using diabetic mice as the experimental model, the scientists transferred a gene for a factor that is required to produce pancreas cells, but this first approach didn’t work as expected. The cells were actually pancreatic-like, but not only insulin-producing cells, but also the kind of pancreatic cells that secrete digestive enzymes. The consequence was that these enzymes started to digest the liver from inside out.

Back to the drawing board, they chose now a factor known as NeuroD which is specific to cells that produce insulin and other hormones. In this case, the experiment were successful. The mice, treated with NeuroD and a growth factor named betacellulin induced a cure in the mice for at least four months after the application.

Besides insulin, the newly produced cells make other hormones including glucagon, somatostatin and pancreatic polypeptide, which may play a role in controlling insulin production and release. The good news is that these cells did not make digestive enzymes.
Clinical tests performed on the treated mice showed that blood sugar is normal. The mice are capable of responding to an increased load of sugar by increasing the production of insulin. After this encouraging results, scientists will look at other factors to generate even more efficient combinations in producing the pancreas-like cells.

Can humans too?

Very often, success in mice does not immediately translate into treatment for people, but the researchers believe that a similar protocol should work in people. The main concern when developing a gene therapy for humans is the vector or virus used to take the gene into the cells. Chan used an adenovirus called “gutless” to introduce genes into cells. Those viruses are among the safest available today for gene therapy and are also very efficient in taking genes into tissues such as that of the liver. Gene therapy researchers are currently trying to develop even safer vectors within the next years.

Other alternatives: islet cell transplantation

Another option for curing diabetes that has gained attention is transplantation of islet cells, the cells that produce insulin in the pancreas. These type of transplants have been performed in patients with most trouble in controlling the disease. As other kinds of transplantation, islet cells transplants require the patient to take immunosuppressive drugs lifelong, with the consequent permanent risk of contracting infections and other problems. Gene therapy lacks this problem. Moreover, investigators think it would be possible to take islet cells from a diabetic patient, treat them in vitro to introduce the deficient genes and then put them back into the patient’s body. This sort of self-transplant would have no need to induce immunosuppression as the cells belong to the same individual.
Source: http://www.bcm.edu/