the concentration of 2 'deoxyadenosine in their plasma and their cells concommitent 
with the transfusion treatment, and up to 20-302 of ADA(-)SCID had temporary 
improvement in lymphocyte numbers and in response to mitogens or allogeneic 
cells. However, the majority of ADA-deficient patients did not have 
substantial improvement with transfusion therapy and some of the patients who 
initially appeared to benefit subsequently failed to respond despite continued 
treatment. None of these patients developed convincing evidence of an 
antigen-specific immune response at any time during the course of their 
transfusion therapy. 
Very recently, another approach to enzyme replacement has been reported. 
Bovine ADA was conjugated to polyethylene-glycol (PEG) and this PEG-ADA was 
given by intramuscular injection to two ADA-deficient patients. The PEG 
apparently greatly prolongs the serum survival of ADA enzyme activity. The two 
patients, who have been treated for less than one year, have had a striking 
Improvement in their biochemical abnormalities and an encouraging Increase in 
Immune function. The period of observation has been too short to be assured 
that the improvement will persist, particularly since the Initial success seen 
in some ADA-deficient patients treated by exchange transfusions was not 
sustained. Furthermore, there has been no evidence for an antigen-specific 
response. Nor Is it known whether or not long-term administration of the PEG 
compound may result in unexpected complications. Nevertheless, this form of 
enzyme replacement therapy does offer an encouraging therapeutic option. We 
feel that its use should not interfere with or preclude the potential for gene 
therapy to provide a more permanent solution to ADA deficiency. 
A final preventative alternative for ADA ( -) SC I D is the use of an 
gnotobiotic environment (i.e., a germ-free bubble). This approach has been 
used for one SCID patient (viz. “David" in Houston. TX.) but simply is not a 
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