Recombinant DNA Advisory Committee- 9/12-13/94 
Dr. Parkman said uptake of cross correcting enzymes varies from disease to disease. Most 
of the classic studies have been done for Hurler syndrome. Dr. Parkman asked the 
investigators to elaborate on data of a study conducted at the University of Minnesota in 
1993 about survival after BMT for patients with Hunter syndrome. How many of these 
patients have a genotype similar to the present proposed study? What was the clinical 
response in this study? Most of the questions have been related to its effect on the 
symptoms of the central nervous system. It has some effects on organomegaly or airway 
obstruction. 
Dr. Parkman agreed with the suggestion of limiting the present study to adults. Unlike 
the study of adenosine deaminase deficiency, there are adult patients available for the 
study of Hunter syndrome. The RAC could consider the question about whether children 
aged 13 to 18 are permissible. Dr. Walters remarked that children are included in the 
familial hypercholesterolemia study. Mr. Capron commented that other diseases are fatal 
to patients in earlier ages, but in the mild Hunter syndrome, patients over 18 years old are 
good candidates for treatment. Dr. Erickson said that the present study will enroll 
patients with adequate mental capacity, and those patients will be able to make an 
informed consent. It is a strong argument that the study should be limited to adolescents. 
Ms. Meyers said that this is a very painful disease and should not exclude children under 
18 years of age. She said that her own 8 year old son was able to make an informed 
consent to participate in a clinical study. 
Ms. Meyers commented that the Informed Consent document should include barrier 
contraception for men as well as for women. Dr. Chase said that since humter syndrome 
is an X-linked recessive trait with very low fitness, it is largely confined to males. Ms. 
Meyers questioned the compensation for research related injuries. She asked the 
investigator to address the ethical aspect of limiting the treatment to 1 year period in case 
efficacy is demonstrated in the course of the study. 
Dr. D. Ginsburg said that alternative treatments for Hunter syndrome are making 
progress. If in the near future BMT shows promise, the children who have enrolled in the 
present gene transfer study might be excluded from other kinds of treatments. This is 
another reason to hold off the proposal to treat children. Ms. Meyers said most orphan 
diseases have very few other research projects going on. Dr. D. Ginsburg noted that the 
use of BMT is a very active area of research. 
Dr. DeLeon said she would include children as suggested by Ms. Meyers since Hunter 
syndrome is a progressive disease. It is easier to assess the outcome of the treatment in 
children whose disease is in the early stage. Dr. Erickson reminded that this protocol is a 
Phase I study, and efficacy is not the major question. Dr. Saha stated he is not asking the 
investigators to give up children, just that the initial effort would be better performed on 
adults. Dr. Ross agreed on doing the initial study on adults. 
Dr. Samulski said that the investigators indicated that they only had resources for 1 year 
experiment, and that it was not good to include children in this short study. Dr. Parkman 
said that from a scientific point of view, it is better to perform a study on adults in order 
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