PEG-ADA: an alternative to haploidentical bone marrow transplantation and an adjunct to gene therapy for adenosine deaminase deficiency.

PEG-ADA is a long-circulating form of adenosine deaminase (ADA) that has been in use for > 8 years as replacement therapy for severe combined immunodeficiency disease due to ADA deficiency. Treatment with PEG-ADA almost completely corrects metabolic abnormalities, allowing the recovery of a variable degree of immune function. Although not normal, the level of function achieved has in most cases been sufficient to protect against opportunistic and life-threatening infections. PEG-ADA has been used as an alternative for patients who lack an HLA-identical bone marrow donor, but are judged to be at too high a risk for undergoing HLA-haploidentical marrow transplantation. To date, mortality and morbidity with PEG-ADA have been less than for the latter procedure. PEG-ADA has also been an important adjunct to attempts to develop somatic cell gene therapy for ADA deficiency, although its continued use poses a problem for evaluation of the benefit of gene therapy. As a true "orphan drug" developed to treat a very small patient population, the cost per patient of PEG-ADA is very high.