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

NCT00004454 | Completed Phase 1

• 3 other identifiers: 199/13577UMN-HUNTERUMN-5P01HD32652
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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.

Conditions

Mucopolysaccharidosis II

Keywords

inborn errors of metabolism; mucopolysaccharidosis; mucopolysaccharidosis II; rare disease

Interventions

lymphocyte gene therapy GENETIC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): lead
• University of Minnesota: collaborator

Study Sites (1)

University of Minnesota Medical School

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Mucopolysaccharidosis II; Metabolism, Inborn Errors; Mucopolysaccharidoses; Rare Diseases

Condition Hierarchy (Ancestors)

X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heredodegenerative Disorders, Nervous System; Carbohydrate Metabolism, Inborn Errors; Lysosomal Storage Diseases; Mucinoses; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Chester B. Whitley

  University of Minnesota

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: October 18, 1999
• First Posted: October 19, 1999
• Study Start: October 1, 1996
• Last Updated: June 24, 2005

Record last verified: 2003-10

Locations

US (1)