Mucopolysaccharidosis II
Conditions
Keywords
inborn errors of metabolism, mucopolysaccharidosis, mucopolysaccharidosis II, rare disease
Brief summary
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.
Detailed description
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.
Interventions
GENETIClymphocyte gene therapy
Sponsors
University of Minnesota
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Study design
Primary purpose
TREATMENT
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Countries
United States
Outcome results
None listed