AGT-181 is a fusion protein containing alpha-L-Iduronidase that is intended to deliver the enzyme peripherally and to the brain, when administered intravenously. This study is a safety and dose ranging study to obtain safety and exposure data, as well as information on the biological activity of the investigational drug.

Inclusion Criteria:

• Male age 18 years or older
• Diagnosis of MPS I (documented fibroblast or leukocyte IDUA enzyme activity level of less than 10% of the lower limit of the normal range of the measuring laboratory)
• Voluntary written consent by patient or legally responsible representative
• All women of childbearing potential and sexually mature males must be advised to use a medically accepted method of contraception throughout the study.
• Negative pregnancy test (females)
• Must not have received ERT for at least 6 weeks prior to AGT-181 treatment
• Must have elevated urinary GAGs if no ERT has been received in the prior 3 months

Exclusion Criteria:

• Refusal to complete baseline evaluations.
• Any medical condition or other circumstances that may significantly interfere with study compliance
• Receipt of an investigational drug within the prior 90 days
• History of diabetes mellitus or hypoglycemia
• Clinically significant spinal cord compression, evidence of cervical instability.
• Known hypersensitivity to alpha-L-iduronidase or any of the components of AGT-181.
• Known to be nonresponsive to standard ERT treatment.
• Previously successful (engrafted) hematopoietic stem cell transplantation that resulted in normalization of urinary GAGs.
• Contraindication for lumbar puncture

Open Label