Recombinant DNA Advisory Committee - 06/7-8/93 
on: (1) the imminent birth of the newborns, (2) the gene therapy safety issues are the 
same as the original protocol, and (3) the prospective benefit to these infants. 
Review-Dr. Smith 
Dr. Smith agreed with the issues discussed by Dr. Post. Dr. Smith recommended the 
RAC should approve the proposed minor modification. 
Review-Dr. Leventhal 
Dr. Leventhal recommended that the proposed minor modification should be approved 
contingent on the following: (1) the diagnosis will be confirmed at birth, (2) there will 
be no maternal contamination of the cord blood, (3) polyethylene glycol (PEG)-ADA 
will be administered, and (4) a portion of the cord blood will be cryopreserved. 
Review-Dr. Walters 
Dr. Walters stated that the investigators have outlined the differences between the 
proposed minor modification and the major amendment that was approved by the RAC 
at its February 1992 meeting: (1) G-CSF will not be administered to the newborns, (2) 
leukapheresis will not be performed to harvest CD34( + ) cells, and (3) the requirement 
for PEG-ADA pretreatment has been omitted. He asked the investigators to respond to 
the following questions: (1) Will PEG-ADA be withdrawn at the discretion of the PI? 
(2) Is bone marrow aspiration in newborns safe and necessary? (3) Are there any 
preclinical studies in which newborn animals have received autologous transduced cells 
obtained from cord blood or placenta? (4) At what point in the pregnancy is fetal ADA 
deficiency detected? Are there alternative therapies? (5) Will a sufficient supply of a 
new stem cell growth factor be available for these patients to be treated in May 1993? 
and (6) Will the LASN or GINaSvADA vector be used to treat these infants? 
Other Comments 
Ms. Meyers questioned whether there are separate Informed Consent documents for 
patients that will be treated at the additional sites outside of the NIH. Dr. Doi asked 
whether transduced cryopreserved CD34( + ) cells have been demonstrated to be as 
effective as transduced fresh cells. In response to Dr. Kohn's statement that the Food 
and Drug Administration (FDA) has determined that the current lot of LASN vector is 
unacceptable for clinical use based on new RCR testing standards, Dr. Post inquired 
about the accuracy of this statement. 
Ms. Grossman suggested that the proposed revision is more than a minor modification 
and should have been treated as an expedited review protocol. She objected to the 
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Recombinant DNA Research, Volume 17 
