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

Inclusion Criteria:

• The presence of MPS I disease as documented by low α-L-iduronidase activity
• Age six years or older.

• The presence of acquired cognitive deficits as demonstrated by:

  1. A score of one standard deviation below mean on IQ testing or in one domain of neuropsychological function (language, memory, or non-verbal ability), OR
  2. Documented historical evidence of a decline of greater than one standard deviation on sequential testing, OR
  3. A score between 0.75 and 1 standard deviation below the mean, AND the cognitive deficit affects daily performance.
• The decline in function is not explainable by other neurological or psychiatric factors.
• Subject and/or guardian willing and able to provide written informed consent.
• Negative urine pregnancy test at screening (non-sterile females of child-bearing potential only)
• Currently using two acceptable methods of birth control as determined by the investigator and willing to continue to use acceptable birth control during their participation in the study (non-sterile females of child-bearing potential who are sexually active only)
• Willing and able to comply with study procedures. For example, the subjects must be able to complete written and computer-based testing. The subjects must be able to lie still in the MRI scanner for at least 40 minutes without sedation.

Exclusion Criteria:

• The subject has undergone hematopoietic stem cell transplantation
• Recent initiation of intravenous Aldurazyme® therapy with less than 6 months of therapy. Subjects who have been receiving Aldurazyme® therapy for more than 6 months, and those who have never received Aldurazyme® therapy, will be allowed to enroll
• Pregnant or lactating, or considering pregnancy
• Receipt of an investigational drug or procedure within 30 days of enrollment
• A condition, medical or other, that prevents participation in the study, including severe auditory or visual impairment, significant lumbar pathology, lumbar catheter, or recent major surgery within 6 weeks that would preclude their ability to participate.
• Infusion reactions to intravenous Aldurazyme® therapy that require ongoing medical intervention, special prophylaxis or altered rate or dose of enzyme administration
• The subject has a programmable VP shunt that is incompatible with the 3 Tesla MRI magnet and is unable or unwilling to undergo shunt revision to a MRI compatible device.
• The subject has another contraindication for MRI, such as nonremovable metal in the body.
• The subject has severely impaired spinal CSF flow, demonstrated by failure of appearance of 99mTechnetium-DTPA in the basal cisterns by 4 hours after intra-lumbar administration.