A rare genetic G6PC3 deficiency that causes inflammatory bowel disease can be successfully treated with bone marrow transplantation, according to researchers at the University of Manchester. Such a disease affects around one in a million people and causes intestinal inflammation and lung infections. The team also showed that in affected patients, white blood cells, so-called neutrophils, trigger inflammation when they are treated with commonly available biological therapiesExposed to intestinal bacteriabecome.
New therapy for inflammatory bowel disease
The patients were treated at the Royal Manchester Children's Hospital, one of the world's leading centers for pediatric bone marrow transplantation, led by Professor Rob Wynn. Dr. Anu Goenka carried out the laboratory work as part of such a doctorate. This has financed both a training grant from the Medical Research Council for clinical research and a grant from the European Society for Pediatric Infectious Diseases (ESPID). G6PC3 is important for sugar metabolism and crucial for the energy supply of neutrophils. If there is a deficiency, the latter can only divide and function with difficulty.
Neutrophils, which produce pus, are used by the body to remove bacteria. This is particularly true in the intestines and lungs. The team examined their function and response to bone marrow transplantation in four children with G6PC3 deficiency-associated disease. The children's inflammatory bowel disease did not respond to other immunotherapies, including steroids and biologics. After treatment, symptoms went into remission in all patients. Three of the patients are now three to four years post-transplant and still in remission.
Promising results
Children with such a deficiency are often diagnosed in the first few years of life. This happens even though some are not diagnosed until they are 11 and 12 years old. Due to difficulties in detecting the disease or transplantation, adults can also be affected. Bone marrow donors are either relatives or members of such a registry. The donated marrow is infused into a vein after chemotherapy. New neutrophils appear approximately 10 days after the transfusion, although the immune system takes between three and four months to recover. Most patients remain isolated on a ward for three to four weeks before going home to isolate for further months. The study was carried out inJournal of Leukocyte Biologypublished.
