Lymphocyte Gene Therapy for Mild Hunter Syndrome 
4.0 RESEARCH DESIGN AND METHODS 
4.1 Selection Of Patients 
Two adults (>18 years of age) and two children (ages 5-18 years) with mild Hunter 
syndrome will be eligible for entry into this clinical trial. The diagnosis of mild Hunter syndrome 
will be determined based upon the following clinical, biochemical, and molecular genetic criteria 
(which will be assessed prior to entry into the study): 
4.1.1 Clinical Criteria 
Patients who will be eligible for this protocol must be 5 years or older at the time of entry 
into the protocol and have the clinical manifestations of mild Hunter syndrome (including the 
characteristic coarse facial features, hepatosplenomegaly, and radiographic evidence of dysostosis 
multiplex). By accepted clinical criteria, individuals with the "mild" form of Hunter syndrome 
have normal intelligence (4, 5); thus, eligibility for entry into this protocol will also require 
documentation of an IQ score of 80 or higher. 
Although eligible candidates will have significant medical problems which merit treatment 
(e.g., respiratory disease, cardiac disease), none must be so severe as to be judged as a strict 
contraindication to the necessary procedures and tests of the protocol (which includes 
plasmapheresis, infusion of cells, and completion of the battery of follow-up studies as outlined 
below). The presence of such severe disease would exclude that patient from entry into the study. 
4.1.2 Biochemical Criteria 
Patients will be found to have (a) pathologically elevated urinary excretion of 
glycosaminoglycans (i.e., heparan sulfate and dermatan sulfate) and (b) deficient iduronate-2- 
sulfatase (IDS) enzyme activity measured in both plasma and leukocytes. 
4.1.3 Molecular Genetic Criteria 
Patients will be determined to have a mutation consistent with mild Hunter syndrome, 
either: (a) a single-base substitution of the coding sequence not previously associated with the 
severe Hunter syndrome phenotype, or (b) an exon-skipping mutation that would allow for 
occasional production of (minimal amounts of) normal protein. 
Conversely, patients with mutations consistent with the severe form of Hunter syndrome 
will be excluded from this study, i.e., those patients with: (a) non-sense mutations resulting in a 
truncated IDS protein, (b) partial or complete gene deletions, and (c) missense mutations 
previously associated with a severe phenotype. 
4.2 Clinical Evaluation Prior To Treatment 
Prior to entry into the study, each patient will have a battery of tests and other evaluations 
(detailed in Appendix A) to determine eligibility for entry into the clinical protocol. The studies 
will also serve as pretreatment 'baseline studies" for subsequent comparison. 
4.3 Stratification .And Randomization - Not applicable. 
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