OBJECTIVES: I. Evaluate the safety and feasibility of treating mucopolysaccharidosis II
(mild Hunter syndrome) by lymphocyte gene therapy.
II. Determine the levels of iduronate-2-sulfatase enzyme in these patients attained by
infusing increasing doses of lymphocytes transduced with a retroviral vector designed for
insertion and expression of this iduronate-2-sulfatase gene (L2SN).
III. Determine the duration of survival of these transduced cells in these patients.
IV. Determine whether monthly infusion of L2SN-transduced lymphocytes accomplishes
metabolic correction (as measured by glycosaminoglycan excretion), decrease in liver or
spleen volume, any therapeutic effect upon cardiac and pulmonary dysfunction, or any other
effects from treatment.
PROTOCOL OUTLINE: Peripheral blood lymphocytes are harvested from patient by apheresis,
stimulated to initiate the growth of T-lymphocytes, transduced with retrovirus L2SN
containing iduronate-2-sulfatase, and reinfused into the patient.
Patients receive 12 monthly infusions of these retroviral-mediated gene transduced
lymphocytes with the first three infusions in a dose escalation format.
Patients are monitored for at least 2 hours after completion of each infusion. Patients are
followed at 1 year after treatment, and then until death.
PROTOCOL ENTRY CRITERIA:
Mucopolysaccharidosis II (mild Hunter syndrome) as defined by the following:
- Characteristic coarse facial features, hepatosplenomegaly, and radiographic evidence
of dysostosis multiplex
- Elevated urinary excretion of glycosaminoglycans in 3 urine specimens
- Deficient iduronate-2-sulfatase enzyme activity as measured in plasma and leukocytes
- Mutation consistent with mild Hunter syndrome must have either: A single base
substitution of the coding sequence not previously associated with severe Hunter
syndrome phenotype OR An exon-skipping mutation that would allow for occasional
production of (minimal amounts of) normal protein
Cardiovascular: No severe cardiac disease
Pulmonary: No severe respiratory disease
- Must have IQ score of 80 or higher
- Effective contraception required of all fertile patients