Recombinant DNA Advisory Committee- 9/12-13/94 
to obtain data on how long the transgene would persist in individuals and how often 
patients have to be treated. Children are not reliable subjects to commit themselves to 
complete the study. Dr. Samulski supported the idea that this study potentially can yield 
data on how long and how frequent gene transfer has to be performed to sustain gene 
expression. 
On the point raised by Ms. Meyers on limiting the study to one year, Dr. Straus said it is a 
sensible decision to inform patients that depending upon outcome, there may or may not 
be further investigation. This point can be more clearly stated in the Informed Consent 
document to avoid false hope from the patients. 
Dr. Chase said that patient’s perception of benefit may be different from scientific 
consideration that no benefit is intended for the present study. Dr. Ross said that she has 
yet to see the revised Informed Consent document that informs the patients when they 
will learn about the outcome of the study. 
Dr. Saha would leave the decision if the study will continue after 1 year period to the 
discretion of the investigators. 
Investigator Response-Drs. Whitley and Mclvor 
Dr. Walters called on the investigators to address the issues raised by RAC members. He 
noted that Dr. Mclvor has in the past served on the RAC and its Human Gene Therapy 
Subcommittee. 
Dr. Whitley said that they have extensive experience in treating the Hurler syndrome, the 
Type I mucopolysaccharidosis, with transplantation of normal bone marrow into children. 
The details of the study have been published. There is not only good somatic response, 
but some preservation of neurologic function. In contrast, BMT has seen some success in 
treating Hunter syndrome, the Type II mucopolysaccharidosis, in terms of organ shrinking 
and airway improvement, but little effect on symptoms of the central nervous system. This 
is the reason to choose this disorder for the present study. 
Dr. Whitley said that patient selection is one of the most difficult issues. Regarding the 
genotype, there are few common gene mutations in this disease except a few hot spots of 
gene mutations, and the genetic mutations do not always predict the phenotypes. So 
relying solely upon genotype analysis is not a good way of selecting patients. There is 
some evidence indicating that patients with mild Hunter syndrome frequently have 
alternative splicing of mRNA of the IDS gene. A majority (99%) of the mRNA produces 
ineffective IDS enzyme, and only about 1% is making functional enzyme. 
The primary patient selection criteria would be some assessment of the clinical severity. 
Even mild Hunter syndrome patients very rarely live beyond the age of 40 years. 
Although the disease appears mild, frequently there are severe internal organ problems. 
The investigators debated among themselves the question of whether to include children 
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Recombinant DNA Research, Volume 20 
