MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate In A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER; CONTINUATION: page of ^ pages. 
The injection of PEG-ADA (polyethylene glycol chemically attached to bovine ADA), provides a 
treatment in which ADA enzyme reaches normal levels In the blood stream. Weekly intramuscular 
Injections of PEG-ADA have improved growth, increased the number of T-lymphocytes and decreased 
the severity of infections in some patients. However, PEG-ADA therapy has not fully restored the 
immune system in most patients. -Many patients have continued to have low numbers of lymphocytes in 
their blood and/or have an increased number of infections requiring antibiotics and/or hospitalization. 
What is Gene Therapy? 
We have investigated the possibility of carrying out a new experimental treatment called gene therapy 
to improve upon the partial immunologic restoration seen with PEG-ADA treatment. The technique 
involves taking blood from your child’s vein and separating out T-lymphocytes in the laboratory. A 
normal ADA gene is inserted into the T-lymphocytes using a process called retroviral-mediated gene 
transfer. The cells with a normal ADA gene would then be transfused back into the child's vein. We then 
will study your child's Immune system to determine if its functioning has improved. We expect that the 
infusion of these ADA-corrected cells may result in a boost to your child’s immunity. We will 
determine this by testing the immune functioning of T-lymphocytes in the blood, the development of 
new positive responses to skin testing and new abilities to make specific antibodies following 
vaccination. Real improvements in these responses may then result in less frequent infections and a 
diminished risk of developing a malignancy. 
The process involved in introducing the ADA gene is accomplished by first inserting the normal ADA 
gene into a vector (an organism that carries material from one cell to another). This vector is 
prepared from a disabled mouse retrovirus. The vector is mixed with the patient’s cells in the 
laboratory. The vector enters the cells and inserts the normal ADA gene into the cells’ genetic material 
(chromosomes). Once inserted, the new ADA gene will survive as long as the cell survives. 
Experiments in our laboratory have shown that T-lymphocytes can be grown from the blood of children 
who are being treated with PEG-ADA. These ADA defective cells can then be treated with the gene 
transfer technique to become ADA-normal T-lymphocytes. The ADA-normal T-lymphocytes behave 
like normal cells and grow for longer periods of time in tests performed in the laboratory. T- 
lymphocytes from children receiving PEG-ADA have been injected into mice (ADA normal) that have no 
functioning immune system. The human ADA defective cells survived and functioned in the mice only if 
they had been gene-corrected using retroviral-mediated gene transfer of the ADA gene. These findings 
suggest that the addition of a normal ADA gene may provide increased immune functioning in addition to 
the benefit obtained from PEG-ADA therapy. 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (1D«4) 
NIH-2514-2 (1(Va4) 
P A : 09-25-0099 
Recombinant DNA Research, Volume 14 
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