Intrathecal Enzyme Replacement for Hurler Syndrome

Study Overview
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Brief Summary
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This protocol will examine whether the enzyme alpha-L-iduronidase (Laronidase), delivered into the spinal fluid of patients with Hurler syndrome at intervals before and after bone marrow transplant, is a safe and effective approach to slow the neurologic degeneration seen in Hurler patients undergoing transplantation.

Detailed Description
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Subjects will receive an infusion of Laronidase into his/her spinal fluid approximately 12 weeks before, 2 weeks before, 100 days after and 6 months after transplant. This procedure is done by lumbar puncture (also called a spinal tap).

Official Title
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Intrathecal Enzyme Replacement Therapy For Patients With Mucopolysaccharidosis Type I (Hurler Syndrome)

Conditions
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Hurler Syndrome

Intervention / Treatment
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* Drug: IRT Laronidase


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with a diagnosis of MPS IH (Hurler syndrome) are candidates for this protocol if they are being considered for hematopoietic stem cell transplantation according the University of Minnesota guidelines. Exclusion Criteria: Patients are less than 6 months old, or older than 3 years of age. There is a history of clinically-severe hypersensitivity to Laronidase. There is a contraindication for repeated lumbar puncture. The family is not willing to undergo the necessary procedures and evaluations inherent in the study. Consent has not been signed for participation in the 2004-09 study of intravenous Laronidase administration.

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 3 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intent-to-Treat<br>All patients who have received at least one dose of Laronidase. | Drug: IRT Laronidase<br>* Laronidase belongs to a class of drugs called enzyme replacement therapies or ERT that provides people with sufficient quantities of an important enzyme that they cannot create on their own. The main ingredient in laronidase is a protein that is identical to a naturally occurring form of the human enzyme alpha-L-iduronidase. Laronidase replaces the missing enzyme alpha-L-iduronidase and restores sufficient enzyme activity to break down GAG buildup. Subjects will receive an infusion of Laronidase into his/her spinal fluid approximately 12 weeks before, 2 weeks before, 100 days after and 6 months after transplant. This procedure is done by lumbar puncture<br>* Other names: Aldurazyme;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To demonstrate the efficacy of intrathecally delivering alpha-L-iduronidase in patients with mucopolysaccharidosis type I in decreasing neurodevelopmental deterioration |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the safety and toxicity of intrathecally delivering alpha-L-iduronidase in patients with mucopolysaccharidosis type I |  | 1 year | 
| To determine brain changes with magnetic resonance imaging |  | 1 and 2 years | 
| To determine neurocognitive changes present in patients with Hurler syndrome |  | 6, 12, and 24 months | 
| To determine cerebral spinal fluid levels of glycosaminoglycans, cytokines and antibodies to Laronidase at baseline and at each point CSF is obtained |  | through 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hurler Syndrome, mucopolysaccharidosis type I, Iduronidase deficiency