Press release issued by Royal Manchester ChildrenÕs Hospital, July 29, 1997 GENE TRANSFER AS AN ATTEMPT TO TREAT HURLER SYNDROME The first Gene Therapy Transplant is to take place at Manchester ChildrenÕs Hospitals NHS Trust this week (expected afternoon of July 30 or morning of July 31). This is the first such procedure to be carried out in the world and is a significant step forward in the treatment of children with Hurler Syndrome. Hurler Syndrome is a genetic disorder which results in the deficiency of an essential enzyme.In affected patients there is an accumulation within the cells of chemical which would, under normal circumstances, be broken down. This accumulation of chemicals stops the cells from working. Most patients are diagnosed in the first year of life. Untreated, the disorder is progressive and leads to a characteristic facial appearance, short stature, joint stiffness, heart disease, enlargement of the liver and spleen and progressive neurological deterioration. Most patients with the severe form of the disease will die before the age of 10 years. By genetic testing, it is now possible in many patients to predict how severely they will be affected. Approximately 100 children with this disorder will be alive within the UK at any one time. In carefully selected cases it is possible to alter the natural history of the disease by bone marrow transplantation (BMT). This protects the nervous system from further damage but many residual problems remain such as bone and joint deformity. Unfortunately, not all patients have a suitable donor and the risk of BMT is high especially if a matched unrelated donor is used. Our experimental therapy involves transferring a normal copy of the defective gene back into the patient using a retroviral vector and their own bone marrow. The procedure involves harvesting the patientÕs own bone marrow and transferring it to the laboratory where it is placed in contact with the virus containing the normal gene. After a series of daily infections over five days, it is transfused back into the patient via a large vein. The bone marrow cells the find their way back to the marrow cavity and re-establish themselves. The patients will be closely monitored after the procedure and after six months it should be possible to assess success or failure. We emphasise that this is an experiment. We have shown that it is possible to do this in the laboratory using bone marrow culture from Hurler patients. This is the first attempt to do this in a patient. It is likely that we will get more questions than answers from this initial attempt. The treatment forms part of a general research programme between the Willink Biochemical Genetics Unit at the Royal Manchester ChildrenÕs Hospital, the Patterson Laboratories, Christie Hospital, Manchester, and the Department of Chemical Pathology, the Women and ChildrenÕs Hospital, Adelaide, South Australia. We are taking the first steps down what we are sure will be along road towards finding an effective cure for this disease and others like it. For further information contact: Linda Roberts Manchester ChildrenÕs Hospitals NHS Trust Hospital Road Pendlebury Manchester M27 4HA UK Tel: +44 (0) 161 727 2220 Fax: +44 (0) 161 727 2370