A Study of Intrathecal Enzyme Therapy for Cognitive Decline in MPS I

Summary

This is a 24-month study of the use of laronidase administered into the spinal fluid to treat cognitive decline in mucopolysaccharidosis I (MPS I). MPS I is a rare genetic condition due to deficiency of the enzyme alpha-l-iduronidase. Laronidase is the manufactured form of the enzyme alpha-l-iduronidase.

MPS I is a heterogeneous disease with several clinical phenotypes ranging from the most severe, Hurler syndrome, to the attenuated forms, Hurler-Scheie and Scheie. Although patients with milder forms of MPS I may not have grossly observable problems with cognition, these patients do have learning difficulties that are apparent in school and with neuropsychological testing. The goal of this study is to evaluate whether intrathecal recombinant human alpha-l-iduronidase (rhIDU) injections can stabilize or improve cognitive decline in individuals with MPS I.

Conditions

• Cognitive Decline
• Mucopolysaccharidosis I
• Hurler-Scheie Syndrome
• Scheie Syndrome
• Lysosomal Storage Disease

Interventions

DRUG

laronidase

For the treatment group, intrathecal rhIDU injections will consist of 3 cc of Aldurazyme® (laronidase) (approximately 1.74 mg) diluted with 6 cc of Elliotts B® solution for a total injection of 9 cc. The diluted enzyme will be administered via a lumbar puncture (IT) on day 0 after baseline assessments. IT injections will be repeated on days 30, 60, and 90. The subsequent doses will be administered at 3-month intervals for a total of 10 doses during the two-year period. Control patients will not receive treatment, lumbar puncture, or placebo, but will undergo all other study procedures and assessments during year one. Control patients will then enter a treatment phase consisting of four IT doses at 3-month intervals.

Sponsors & Collaborators

• The Ryan Foundation

  collaborator OTHER

• BioMarin Pharmaceutical

  collaborator INDUSTRY

• Rare Diseases Clinical Research Network

  collaborator NETWORK

• National Center for Advancing Translational Sciences (NCATS)

  collaborator NIH

• National Institute of Neurological Disorders and Stroke (NINDS)

  collaborator NIH

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

  collaborator NIH

• University of Minnesota

  collaborator OTHER

• University of California, Los Angeles

  collaborator OTHER

• Patricia I. Dickson, M.D.

  lead INDIV

Principal Investigators

• Agnes Chen, MD · Los Angeles Biomedical Institute at Harbor-UCLA

• Patricia I Dickson, MD · Los Angeles Biomedical Institute at Harbor-UCLA

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

CROSSOVER

Eligibility

Min Age

6 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2009-06-30

Primary Completion

2015-04-30

Completion

2015-04-30

Countries

• United States

Study Locations