Enzymes as agents for the treatment of disease

The replacement of genetically deficient enzymes in patients with inherited metabolic disorders by infusion of purified enzymes or by organ transplantation has had very limited success, although good results with bone marrow transplantation have been obtained in some patients with mucopolysaccharidosis, Gaucher disease and inherited immunodeficiency diseases. Genetic engineering of the patient's lymphocytes may ultimately render these approaches redundant, at least for some of these diseases. Treatment of chronic pancreatic insufficiency and of disaccharidase deficiency with oral enzymes can be very effective; therapy can be monitored in the latter by measuring the breath hydrogen excretion and in the former by a range of tests of which stool chymotrypsin assay is the most convenient. Treatment of acute myocardial infarction by intracoronary perfusion of thrombolytic enzymes can improve both cardiac function and long-term survival if given early enough. Successful reperfusion can be identified by changes in the kinetics of serum enzyme release and clearance, especially for the isoenzymes and isoforms of creatine kinase. In cancer chemotherapy, L-asparaginase has long been a useful adjunct in the treatment of acute lymphoblastic leukemia, but recent experience suggests a role in acute nonlymphoblastic leukemia as well.