Extension Study of Intrathecal Enzyme Replacement Therapy for MPS I

An Extension Study of Intrathecal Enzyme Replacement Therapy for Spinal Cord Compression in Mucopolysaccharidosis I

This is a one-year extension study of the use of laronidase into the spinal fluid to treat spinal cord compression in mucopolysaccharidosis I. Mucopolysaccharidosis I is a rare genetic condition due to deficiency of the enzyme alpha-l-iduronidase. Spinal cord compression occurs in this condition due to accumulation of material called glycosaminoglycans (GAG). Laronidase is the manufactured form of the enzyme alpha-l-iduronidase that is deficient in mucopolysaccharidosis I patients. The aim of this study is to determine whether laronidase is safe and effective when given into the spinal fluid as a potential non-surgical treatment for spinal cord compression due to mucopolysaccharidosis I disease. Funding Source -- FDA OOPD

Enzyme replacement therapy (ERT) has been developed for mucopolysaccharidosis I (MPS I), a lysosomal storage disorder. ERT helps many physical ailments due to the disease, but does not treat the central nervous system, due to inability to cross the blood brain barrier. Our purpose is to test delivery of ERT to the spinal fluid via intrathecal injection in patients with MPS I. In this pilot study, we will use recombinant human α-L-iduronidase administered intrathecally once per month for four months to individuals with the Hurler-Scheie and Scheie forms of MPS I and spinal cord compression. If successful, intrathecal delivery could represent a practical, straightforward method of treating central nervous system disease due to lysosomal storage.

Inclusion Criteria:

• Hurler-Scheie, Scheie form of MPS I, or Hurler 2 years after hematopoietic stem cell transplantation

  • Spinal cord compression
  • Has received intrathecal laronidase previously with good response and no significant safety concerns
  • Age greater than 8 years
  • Able to provide legal informed consent
  • Aware of clinical treatment option of observation without treatment or surgical decompression
  • Negative urine pregnancy test at screening (nonsterile females of child-bearing potential who are sexually active only)

Exclusion Criteria:

• Severe (Hurler) form of MPS I
• Desires surgical or medical treatment of spinal cord compression
• Spinal cord compression that warrants immediate surgical intervention
• Pregnancy or lactation
• Hematopoietic stem cell transplantation within 2 years of study enrollment
• Receipt of an investigational drug within 30 days of enrollment
• Infusion reactions to laronidase that required medical intervention, prophylaxis, or altered enzyme administration
• Significant anti-iduronidase antibody titer
• Recent initiation of intravenous laronidase (within past 6 months)
• Presence of cervical subluxation or similar external pathology as the major cause of cord compression symptoms for which surgical intervention should be immediately undertaken