BETHESDA, Md -- November 6, 2009 -- Researchers have discovered that mutations in either of 2 related genes cause a severe and rare form of inflammatory bowel disease (IBD) in young children. The research is will appera in the November 19 issue of the New England Journal of Medicine.
Discovery of the genetic mutations allowed the researchers to successfully treat 1 of the study patients with a bone marrow transplant. The patient, who had not responded to other therapies, showed dramatic improvement following the bone marrow transplant and has remained in remission from IBD for more than 1 year.
The collaborative study included researchers from the National Center for Biotechnology Information (NCBI) at the National Institutes of Health, Hannover Medical School in Germany, University College London (UCL) in the United Kingdom, and several other institutions.
"This is an excellent example of how discovery of causative genes and mutations can enable clinicians to go from bench to bedside for an informed treatment of patients," said Christoph Klein, MD, Medical School of Hannover, Hannover, Germany, who led the diagnosis and treatment effort.
The successful treatment of the patient in this study built upon a well established treatment approach: that bone marrow transplants can be curative in genetic disorders where the affected gene is normally active in cells derived from the bone marrow.
Because of the risks associated with bone marrow transplants, they are used only in cases of severe diseases, where the potential benefits outweigh the risks. Patients with the IBD caused by the genetic mutations identified in this research have very severe disease that meets this general criterion, though each case must be evaluated individually. The study patient's matched donor was a healthy sibling, which is the preferred approach, but bone marrow transplants also can be done using more distantly related or unrelated matched donors.
The mutated genes identified in the study encode the proteins IL10R1 and IL10R2, which act together to receive signals from the cytokine interleukin 10 (IL10). IL10 plays a crucial role in keeping the body's inflammatory responses in check. When either IL10R1 or IL10R2 is mutated, the signals from IL10 cannot be received, and the resulting inflammation causes tissue damage, especially in the gastrointestinal system.
"This discovery is a milestone in research on inflammatory bowel disease, and will enable us to gain further insights into the physiology and immunity of the intestine," said Erik Glocker, MD, Univeristy College London, London, United Kingdom, who found the first mutation in IL10R2 identified in the study.
SOURCE: National Institutes of Health
E-Mail this DGNews to a colleague
