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Immunology

Double attack

Association of chemotherapy and adult stem cells helps to control juvenile diabetes

MIGUEL BOYAYANTo use the term cure is exaggerated and premature, but an experimental treatment that administers large doses of chemotherapy followed by a transplant of adult stem cells originating from the bone marrow of the patient himself has achieved encouraging results in controlling type 1 diabetes mellitus, also called juvenile or insulin dependent diabetes, an immunological disease that affects about 1 million Brazilians.

Of the 11 patients, all adults, submitted to the two procedures at the Cell Therapy Center (CTC) of the Ribeirão Preto School of Medicine, linked to the University of São Paulo, ten showed significant progress: eight freed themselves from the daily need to take insulin – one of them has remained in this healthy condition since March 2004, almost two years ago – and two started being given only half of the dose of this hormone that they needed before to control the disease.

“We cannot talk about a cure”, ponders immunologist Júlio Cesar Voltarelli, who is heading up this line of research. “We do not know whether the benefic effects are lasting, whether they are going to persist for three, four or five years.” Only one patient did not show any improvement, precisely the first one to be submitted to the alternative therapeutic scheme, back in November 2003.

The researchers believe that this case did not behave in the same way as the others because corticoids were used to prevent allergic reactions to the medicines used in the transplant, and it is known today that this type of drug does not give good results in diabetics. The other patients were given other classes of medicines, apparently more effective in these cases.

Even though the benefits of the new approach persist in the long term, the treatment will hardly be established as the cure for the disease. The procedure is aggressive, lengthy (it goes on for some three months) and very expensive. The chemotherapy plus the transplant of the adult stem cells take a long time and have an estimated cost of at last R$ 30 thousand and, according to Voltarelli, could not be adopted as the standard therapy for taking care of all the patients with this kind of diabetes.

“Nevertheless, the researches indicate a route that we may follow to combat the mechanism that causes type 1 diabetes”, explains Marco Antonio Zago, the coordinator of the CTC in Ribeirão Preto, one of the ten Research, Innovation and Diffusion Centers (Cepids) supported by FAPESP. Like lupus, multiple sclerosis and other ailments, type 1 diabetes is an autoimmune disease, usually diagnosed in childhood or in adolescence. In other words, its primary cause is due to the malfunctioning of the defense cells of the organism itself.

The immunological system starts to destroy the beta cells of the pancreas, responsible for the production of insulin, the role of which is to remove the glucose from the blood. Without the capacity for producing naturally this hormone that regulates the entry of sugar into the cells, the young diabetic becomes a hostage to daily insulin shots.

The therapeutic approach proposed by the Brazilian researchers has the objective of combating the process of an inflammatory attack on the tissue of the pancreas with large doses of immunodepressant as soon as the juvenile diabetes is discovered (all the patients that are taking part in the CTC’s study had been given a diagnosis of the disease at least six weeks ago).

In the initial stage of type 1 diabetes, the scientists say, a small quantity of beta cells is still left over that is capable of generating insulin, which, if it is preserved, and provided that the immunological disorder is overcome, can multiply and give back to the organism its capacity for generating insulin.

Transplant
One should make no mistake about the role of the adult stem cells in the alternative therapy. They come into the treatment because the chemotherapy employed is so aggressive that, besides attacking the cause of the immunological inflammation, it dismantles the whole defense system and destroys the diabetic’s bone marrow, as in the more toxic treatments against certain kinds of cancer.

For this reason, the doctors resort to the transplant of stem cells, which allows the patient to reconstitute his bone marrow and also his immune system. The hypothesis has not been completely discarded that the stem cells in themselves play some role favorable to the multiplication of the pancreas’s remaining beta cells. But this is definitely not the line of thought that governs its use in experimental therapy against juvenile diabetes.

“Our idea is to act chemically as soon as possible to preserve the organism?s natural capacity for generating beta cells and to use it against the disease”, Voltarelli explains. “We use the stem cells with the intention of recomposing the patients’ bone marrow.” Nothing guarantees that the benefic action of the treatment against type 1 diabetes is not fleeting.

As in the case of cancer, it is prudent to wait five years without the disease before pronouncing the word “cure”. Even so, once again as happens with some tumors, even after 60 days have elapsed, there are no guarantees that another immunological attack may not happen again, unleashing once more the progressive destruction of the beta cells. It is true that, in theory, if the patient is still clinically well, the doctors could once again resort to the chemotherapy and the transplant of stem cells to fight the diabetes.

Even with these restrictions, the results achieved are sufficiently encouraging to stimulate the continuity of this line of clinical research. The next step for the researchers from the CTC – who can count on financial support from the Financier of Studies and Projects (Finep), the National Council for Scientific and Technological Development (CNPq) and the Centralized Health system (SUS) – may perhaps be to test the candidate to therapy on children who have just been given the diagnosis of type 1 diabetes.

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