Enzyme replacement and other biochemical approaches to the therapy of adenosine deaminase deficiency.
Addition of adenosine deaminase (ADA) restored in vitro responses of lymphocytes from a patient with ADA deficiency and severe combined immunodeficiency (SCID). Enzyme replacement therapy, using red blood cells as a source of encapsulated human ADA, restored both T and B cell function in this patient. Ten other ADA--SCID patients have been treated with this form of enzyme replacement and five have responded to therapy. Lymphocytes from ADA--SCID patients treated with enzyme replacement become immunocompetent but remain enzyme deficient. Studies of these cells provide evidence supporting both cyclic AMP- and dATP-mediated immunosuppressive mechanisms in ADA--SCID. These observations suggest that inhibition of cyclic AMP synthesis and/or deoxycytidine (and possibly thymidine) supplementation may be useful new biochemical approaches to the therapy of ADA--SCID.
D000241:Adenosine / Q000494:pharmacology; D000243:Adenosine Deaminase / Q000172:deficiency*; D001402:B-Lymphocytes / Q000276:immunology; D001803:Blood Transfusion; D000242:Cyclic AMP / Q000494:pharmacology; D003839:Deoxyadenosines / Q000494:pharmacology; D003841:Deoxycytidine / Q000494:pharmacology; D017707:Erythrocyte Transfusion; D004912:Erythrocytes / Q000201:enzymology; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000201:enzymology / Q000628:therapy*; D007223:Infant; D007422:Intestines / Q000201:enzymology; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000201:enzymology; D008297:Male; D009700:Nucleoside Deaminases / Q000172:deficiency*; D011743:Pyrimidines / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000276:immunology; D013936:Thymidine / Q000494:pharmacology
D003839:Deoxyadenosines; D011743:Pyrimidines; D003841:Deoxycytidine; D000242:Cyclic AMP; D009700:Nucleoside Deaminases; D000243:Adenosine Deaminase; D000241:Adenosine; D013936:Thymidine