Mucopolysaccharidosis I, Lysosomal Storage Diseases, Spinal Cord Compression
Conditions
Keywords
mucopolysaccharidosis, Hurler-Scheie, Scheie, laronidase, spinal cord compression, central nervous system, enzyme replacement therapy, intrathecal, LA Biomed
Brief summary
The investigators are studying the use of enzyme replacement therapy into the spinal fluid for treatment of spinal cord compression in the Hurler-Scheie and Scheie forms of mucopolysaccharidosis I (MPS I). 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
0.58 mg/ml solution for intravenous injection, dose 1.74 mg intrathecally once per month for four injections.
Sponsors
The Ryan Foundation
University of California, Los Angeles
FDA Office of Orphan Products Development
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, of Hurler 2 years after hematopoietic stem cell transplantation * Spinal cord compression * 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 (non-sterile females of child-bearing potential only) * Currently using two acceptable methods of birth control (non-sterile females of child-bearing potential who are sexually active only) * Willing and able to comply with study procedures
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 each month | four months |
Secondary
| Measure | Time frame |
|---|---|
| improvement in spinal cord compression due to mucopolysaccharidosis I | four months |
Countries
Finland, United States
Outcome results
None listed