Spinal Cord Compression, Mucopolysaccharidosis I, Hurler-Scheie Syndrome, Scheie Syndrome, Lysosomal Storage Disease
Conditions
Keywords
mucopolysaccharidosis, Hurler-Scheie, Scheie, laronidase, spinal cord compression, central nervous system, enzyme replacement therapy, intrathecal
Brief summary
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
Detailed description
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.
Interventions
DRUGlaronidase
1.74 mg intrathecally every 1-3 months for 1 year
Sponsors
The Ryan Foundation
Patricia I. Dickson, M.D.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
8 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| safety of intrathecal enzyme treatment by blood and spinal fluid tests; improvement or stabilization in neurologic signs and symptoms of spinal cord compression | 1 year |
Countries
Finland, United States
Outcome results
None listed