Breakthrough in Fighting Pompe Disease

Adding a third anti-cancer agent to a current drug cocktail appears to have contributed to dramatic improvement in three infants with the most severe form of Pompe disease -- a rare, often-fatal genetic disorder characterized by low or no production of an enzyme crucial to survival. Duke researchers previously pioneered the development of the first effective treatment for Pompe disease via enzyme replacement therapy (ERT). ERT relies on a manufactured enzyme/protein to act as a substitute for the enzyme known to be lacking in patients with a particular disease. In Pompe disease, ERT has been found to reduce heart and muscle damage caused by the absence of the enzyme. In the new study, appearing online on Oct. 11, 2012, in Genetics in Medicine, the Duke team, and collaborators, added a new step to the therapeutic regimen to address complications suffered by a subset of infants with Pompe disease who are treated with ERT. Some infants with Pompe disease who have certain combinations of genetic mutations develop a severe immune response to ERT. Very high levels of antibodies become directed against the enzyme and greatly reduce its therapeutic effect, leading to rapid clinical decline and death. In a January 2012 publication in Genetics in Medicine, the researchers reported success in preventing the immune rejection in Pompe infants who were just beginning ERT. They treated them with a drug cocktail that included low doses of the cancer chemotherapy drugs rituximab and methotrexate, plus the immune booster gammaglobulin to prevent the immune response to the ERT.