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Basque Research Elhuyar - Zientzia

BASQUE RESEARCH
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Mª Isabel Solana García
Universidad de Navarra
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(+34) 948425600
Universidad de Navarra

2008/2/27

The cause of effectiveness has been discovered for a cirrhosis treatment that has been shown to be useful in 40% of patients

Scientists of the Center for Applied Medical Research (CIMA) of the University of Navarra have discovered the molecular mechanism responsible for the effectiveness of an existing treatment for primary biliary cirrhosis, which combines two substances in order to produce an effect that does not result from either substance separately. The discovery involved the role played by the AE2 protein when the patient is treated with a combination of ursodeoxycholic acid (UDCA) together with glucocorticoids. The research results were recently published in The Journal of Clinical Investigation.

The origin of primary biliary cirrhosis (PBC)-which mostly affects middle-aged women-is still not understood. This pathology is associated with autoimmune phenomena, damage to the biliary vessels of the liver, and a reduction in the production of bile.

In Spain more than 1,000 cases are diagnosed each year, and the total number of patients worldwide is greater than 15,000. Dr. Juan Francisco Medina, Director of the Laboratory of Molecular Genetics of the CIMA, explains that in the present day the diagnosis of this disease, which is generally detected early, permits treatment with UDCA, which is effective in over half of the patients. However, nearly 40% of PBC patients do not respond satisfactorily to monotherapy with UDCA. Therefore, we looked for a combined treatment, and discovered that the combination of UDCA with glucocorticoids was a promising treatment for this group of patients. Those who suffer from this type of cirrhosis have a deficit of AE2, which is the protein for the secretion of bicarbonate in the bile.

The possibility of more cures with fewer transplants

The originality of this recently-published research article consists in relating, for the first time, the combined treatment with UDCA and glucocorticoids with a greater quantity of bicarbonate in the bile, and an improvement of the production of bile by the liver. Specifically, experiments in animal models and cell cultures demonstrate that only the combined treatment with UDCA and glucocorticoids increases the genetic expression of the human protein AE2 in the liver.

Based on available data, Dr. Medina considers that it is advisable to use combined treatment in those cases which present a poor response to monotherapy with UDCA. He proposes the use of a corticoid such as budesonida, which has fewer side effects than cortisone and prednisone. If, for fear of side effects, we allow the disease to progress, it is very probable that the only treatment will be a transplant. On the other hand, if this treatment option is confirmed as successful, it could reduce the number of transplants required in order to save the lives of patients.

The article, published in The Journal of Clinical Investigation, is the work of the team at the CIMA of the University of Navarra directed by Dr. Medina; the other members of the team are Fabián Arenas, Isabel Hervías, Miriam Úriz, Ruth Joplin and Jesús Prieto.

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