Recombinant DNA Advisory Committee - 06/7-8/93 
explanation of long-term follow-up, a request for autopsy in the event of death, 
protection from the media, and a statement informing patients that although they may 
receive no direct benefit from the protocol, knowledge may be gained that will benefit 
others. The motion passed by a vote of 15 in favor, 0 opposed, and 4 abstentions. 
XI. ADDITION TO APPENDIX D OF THE NIH GUIDELINES REGARDING A HUMAN 
GENE THERAPY PROTOCOL ENTITLED: RETROVIRAL MEDIATED TRANSFER 
OF THE cDNA FOR HUMAN GLUCOCEREBROSIDASE INTO HEMATOPOIETIC 
STEM CELLS OF PATIENTS WITH GAUCHER DISEASE /URS. KARLSSON, 
DUNBAR AND KOHN 
Review-Dr. Haselkom 
Dr. Walters called on Dr. Haselkom to present his primary review of the protocol 
submitted by Drs. Stefan Karlsson and Cynthia Dunbar of the NIH, Bethesda, Maryland, 
and Dr. Donald B. Kohn of Childrens Hospital of Los Angeles, Los Angeles, California. 
Dr. Haselkom stated that his general comments regarding gene therapy for Gaucher 
disease that he provided during the review of Dr. Barranger's protocol are also 
applicable to this protocol. This protocol has the potential to produce results as 
dramatic as those observed in the ADA gene therapy protocol. One major concern 
regarding this protocol is that it involves two institutions, the NIH and Childrens 
Hospital of Los Angeles. Two different protocols are described, one using bone marrow 
cells and the other using peripheral blood cells. Although the protocol is for 10 patients, 
it is unclear how many patients will be treated at each institution and how the choice of 
target cells to be transduced will be determined. Dr. Haselkom stated his concern that 
the in vivo enzyme levels are not very significant with the proposed vector. Enzyme 
levels were significantly higher using other vector constructs. Dr. Haselkom stated that 
all of his other concerns have been adequately addressed by the Pis. 
Review-Dr. Motulsky 
Dr. Motulsky stated that Gaucher disease is a recessive disease that affects Jewish 
people of European origin with a substantial frequency of 1 in 500. There is tremendous 
variability in the clinical manifestations of this disease. The correlation between 
glucocerebrosidase (GC) enzyme activity and clinical severity is not predictable. Even 
with the most common mutation of Type I Gaucher disease (nucleotide 1226), there is 
considerable variation in clinical severity. How will this variability affect patient 
selection? Will previous enzyme therapy interfere with determining the success of the 
gene therapy procedure? The investigators have explained that GC expression by 
transduced cells can be distinguished from the activity of the exogenous enzyme. The 
other concerns about preclinical studies and CD34( + ) cell transplantation without 
myeloablation were adequately addressed by the PI. Several specific minor suggestions 
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