Recombinant DNA Advisory Committee - 06/7-8/93 
Review- Dr. Carmen 
Dr. Carmen stated that Gaucher disease appears to be a paradigm affliction made to 
order for gene therapy. He recognized the similarity between this disease and ADA 
deficiency in which the transduced cells have been observed to have growth advantage in 
engrafted bone marrow, therefore, minimizing the need for myeloablation. Data suggest 
that even a low level of GC enzyme expression may be sufficient to ameliorate the 
condition. He recommended that the protocol be approved. 
Other Comments 
Dr. Smith expressed concern about the need for myeloablation and questioned whether 
Cytoxan is an adequate ablative regimen for bone marrow transplantation. Dr. 
Leventhal commented that patients receiving transduced CD34( + ) cells without 
myeloablation will have other treatment options if engraftment is not successful. 
In response to Ms. Grossman's critique, Dr. Motulsky stated that as a medical geneticist, 
he is not in agreement with her comments about the validity of Gaucher disease as a 
candidate for gene therapy. Gaucher disease is an ideal candidate for gene therapy since 
enzyme replacement is expensive and the treatment has to be continually repeated. Ms. 
Meyers said that the Informed Consent document should include the following: (1) a 
suggestion that contraception should be used by males and females, and (2) a request for 
autopsy. Ms. Meyers questioned why patients under 18 years old are excluded from 
participation in this study. 
Responding to Dr. Haselkom's question. Dr. Miller stated that the two vectors proposed 
for the two Gaucher protocols are functionally identical. Both vectors are based on the 
Moloney murine leukemia virus, and produce only the GC enzyme without other vector 
proteins including gag. Dr. Haselkom suggested that additional in vitro experiments 
should be submitted in which the two Gaucher vectors are directly compared in human 
hematopoietic cells. Dr. Krogstad expressed concern that an immune response might be 
generated against the GC enzyme. Dr. Parkman commented that most patients will be 
tolerant to gene expression although there have been a few reported instances of 
antibody responses against the recombinant enzyme. Dr. Parkman noted that the 
recombinant enzyme differs from the cellular enzyme in protein glycosylation. 
Investigator Response-Dr. Barranger 
Responding to the question of myeloablation, Dr. Barranger explained that the first two 
patients will be treated with genetically corrected CD34( + ) cells obtained from 
peripheral blood to assess whether significant engraftment is achieved without 
myeloablation. GC enzyme activity will be measured in the peripheral blood leukocytes 
Recombinant DNA Research, Volume 17 
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