Phase I/II Study of Retroviral-Mediated Transfer of Iduronate-2-Sulfatase Gene Into Lymphocytes of Patients With Mucopolysaccharidosis II (Mild Hunter Syndrome)

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:

--Disease Characteristics--

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

--Patient Characteristics--

Cardiovascular: No severe cardiac disease

Pulmonary: No severe respiratory disease

Other:

• Must have IQ score of 80 or higher
• Effective contraception required of all fertile patients