Lysosomal Disease Network (LDN6719) Immune Response to Intrathecal Enzyme Therapy in Mucopolysaccharidosis 1 Patients

In this study we characterized the immune response to intrathecal (IT) recombinant human alpha-L-iduronidase (rhIDU) in mucopolysaccharidosis I (MPS I) subjects with spinal cord compression who had been previously treated with intravenous rhIDU. Concentrations of specific antibodies and cytokines were measured in serum and cerebrospinal fluid (CSF) collected before monthly IT rhIDU infusions. These serologic findings were compared with clinical adverse event (AE) reports to establish temporal correlations with clinical symptoms. We found that IT rhIDU was generally well tolerated in the subjects studied although one subject had moderate to severe clinical symptoms and serologic abnormalities consistent with an immune response.

• Study Design:
  • Clinical Trial
• Study Type:
  • Observational
• Total number of consented subjects: 5
• Subject Sample Telemetry Report (SSTR)

Samples were taken from participants in the following four studies:

• MIRC-001 (NCT 00215527, P. Dickson, PI): This is a pilot, 4-month study of 1.75 mg IT laronidase (recombinant human alpha-L-iduronidase) given monthly via lumbar spinal tap to MPS I patients age 8 years and older with spinal cord compression.
• MIRC-001 (100) (NCT 00786968, P. Dickson, PI): This is an extension study for MIRC-001. Subjects with good response to IT laronidase defined by improvement in any outcome measure and no safety concerns receive 12 months of additional therapy at 30 to 90 day intervals.
• MIRC-002 (NCT 00852358, P. Dickson, PI): This is a 1-year randomized controlled study followed by 1-year open label phase of 1.75 mg IT laronidase given at 30 to 90 day intervals to MPS I patients age 6 years and older with cognitive impairment or decline.
• MT2007 (NCT 00638547, P. Orchard, PI): This is a 1-year study of 0.05 mg/kg IT laronidase given at 90 day intervals to MPS I Hurler patients age 0.5-3 years in conjunction with weekly 0.58 mg/kg IV laronidase and hematopoietic stem cell transplantation.

• Study Activated September 24, 2010
• First Accrual (chart review): September, 2010

• Primary Phenotype: Mucopolysaccharidosis I
• Lysosomal Storage Diseases

• BioProject
• PubMed
• MeSH
• PMC
• Clinical Trials
  • NCT00852358

• Study Chairs
  • Moin Vera, MD, PhD. Los Angeles Biomedical Research Institute at Harbor UCLA Medical Center, Torrance, CA, USA.
• Participating Site Principal Investigators
  • Jeffrey Krischer, PhD. Data Management and Coordinating Center, University of South Florida, Tampa, FL, USA.
• Current Funding Sources
  • U54-NS065768. National Institutes of Health, Bethesda, MD, USA.