Recombinant DNA Advisory Committee- 9/12-13/94 
patients with cell infusion are all well established procedures, and there can be some hope 
of efficacy. Dr. Erickson would recommend approval. But he would like to limit the 
patients population to adults that can give informed consent. There are enough of those 
patients for a trials of 4 or 5 patients. 
Review-Dr. Saha 
Dr. Saha agreed that Hunter syndrome is an excellent target disease for gene therapy. 
Most of the affected patients will be males. He asked several questions. (1) Patient 
selection. The patients with mild Hunter syndrome have a life expectancy of 30 to 40 
years. Dr. Saha asked if the more severe Hunter syndrome patients are more appropriate 
target for this initial Phase I study. The mild patients can be treated after the efficacy and 
safety questions have been resolved. (2) Number of patients in the study. The study will 
involve 2 children and 2 adults. The numbers are too small, and he suggested to target 
the adults in the first trial to have 4 adults or at least 3 adults. (3) Transduction efficiency 
of lymphocytes. The transduction efficiency of lymphoblastoid cell lines in the preclinical 
studies is very good. The transduction rate of the peripheral blood lymphocytes without 
G418 selection as proposed in the protocol is quite low. The investigator responded in 
writing that the peripheral blood lymphocytes cannot be cultured for longer than 3 to 4 
weeks to allow G418 selection. G418 inhibits lymphocyte growth. Dr. Saha said that 
based on the present state of art of transduction, he has some reservation about efficacy 
of gene transfer to the patients. (4) Vector rearrangement in the transduced cells in 
patients. The investigator needs to elaborate on it. (5) Data of RCR testings. Dr. Saha 
questioned if the testing data was from 5 ml of supernatant not the 100 ml patient dose 
required by the RAC and FDA 
Review-Dr. Ross 
Dr. Ross agreed with other reviewers that the present protocol will be better to study 4 
adults rather than to include children. She has questions about appropriate dosage of the 
gene-modified cells for adults and children. The present protocol calls for cell infusion to 
patients every month for a total of 12 months. Dr. Ross said it is very difficult to keep 
young children for such a prolonged study. The children, after consenting to enter the 
study, may regret later that they had to spend such a prolonged period of time to the 
study. For these reasons, Dr. Ross would recommend limiting the study to adults. 
Other Comments 
Dr. Doi asked about the validity of the idea of transducing lymphocytes to correct for 
lysosomal storage diseases. Dr. Erickson said that the whole basis of the idea is that the 
lysosomal enzymes released from the transduced lymphocytes will be taken up by other 
cells. The alternative BMT treatment does not help the symptoms of the central nervous 
system in classic Hunter patients since the IDS enzyme released from lymphocytes cannot 
cross the blood brain barrier. The overall approach is similar to the treatment of Gaucher 
disease. But Dr. Erickson was not impressed by the cross correction data presented by the 
investigators. 
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Recombinant DNA Research, Volume 20 
