Liver transplantation in parts
Cell therapy instead of liver transplantation
Vladimir Fradkin, Deutsche Welle
Violation of the cycle of urea formation is a rare, but extremely severe congenital disease. Until now, only liver transplantation could help newborn patients, but now German doctors have offered an alternative.
The hereditary disease, which will be discussed today, is quite rare, but extremely severe: out of about 150 babies a year born in Germany with a violation of the urea cycle, half do not live up to a year. We are talking about a birth defect associated with a deficiency of one of the enzymes involved in the biosynthesis of urea. Urea is the end product of protein metabolism, it is synthesized in the liver from ammonia and excreted in the urine.
It is clear that this process is very important for the body, and any violations of it cause ammonia poisoning. Michael Ott, professor at the Graduate School of Medicine in Hanover, says: "Ammonia is a cellular poison capable of overcoming the blood–brain barrier. As a result, severe neurological lesions occur, which manifest themselves both in a weakening of mental abilities and in a violation of motor functions."
Cell transplantation in small portions
This congenital disease is incurable, so the only way to save a patient's life is a liver transplant. However, such an operation is associated with a high risk and is fraught with severe adverse reactions, even when it comes to adults, what can we say about newborn babies.
The way out of this tragic situation was suggested to Professor Ott by experiments on animals: the scientist found that in order to start the mechanism of urea synthesis, it was not necessary to transplant the entire donor liver entirely or at least a significant fragment of it, sometimes it was quite enough to transplant only a relatively small colony of cells. So the idea of cell therapy was born. The transplanted cells of the donor liver are in a special plastic bag and enter the patient's liver via a catheter through a vein. There they disperse and take root.
Professor Ott explains: "We thought and decided that we should inject quite a lot of cells – a total of 600 to 700 million. At the same time, we tried to avoid the formation of blood clots and similar complications. Therefore, we divided the total contents of the pouch into portions and administered these portions evenly for 10 days. We believed that this would reduce the risk of complications, and indeed, so far we have not registered any complications associated with the introduction of donor cells in these children."
Impressive clinical effectsThe cells obtained from one adult donor are enough for seven infants suffering from severe urea cycle disorders.
Although such cell therapy can replace only about four percent of diseased liver tissue with healthy donor cells, it has nevertheless proved to be extremely effective.
As Professor Ott says: "The clinical effects were impressive. All patients, without exception, were in very serious condition, with extremely high levels of ammonia in the blood, sometimes exceeding 1000 micromoles per liter. And in all these cases, we managed to quickly stabilize the condition of patients and reduce the level of ammonia in the blood to normal. Such success prompted us, of course, to work on improving this therapy with a vengeance."
As a rule, the level of ammonia in the blood returned to normal – and it is in children from 40 to 80, in newborns up to 200 micromoles per liter - a day or two after therapy. In total, 8 children have undergone such treatment so far, this number should be increased to 16 within this stage of clinical trials. The first patients were treated in Hanover and Padua, and in the last year and a half all research in this direction has been concentrated at the University of Heidelberg, at the Center for Pediatric and Adolescent Medicine.
Parents have a choiceInitially, this therapy was conceived as temporary, "intermediate", that is, it was only supposed to help the newborn survive until he could be transplanted a donor liver at the age of about six months.
But the cell transplantation turned out to be so successful that the parents of the patients now faced the question of whether this very liver transplantation was needed at all.
Professor Ott says: "This is now a completely new opportunity. The parents seemed to have a choice: decide in favor of donor liver transplantation or wait and see how successful cell therapy will be. I think this is a great progress."
However, the most important question remains open: can such cell therapy cure a sick child once and for all, or is it only able to delay liver transplantation, which sooner or later will become inevitable? The answer to this question will be possible to get no earlier than in a few years.
Portal "Eternal youth" http://vechnayamolodost.ru30.06.2011