Immune response to intrathecal enzyme replacement therapy in mucopolysaccharidosis I patients

Moin Vera, Steven Le, Shih Hsin Kan, Hermes Garban, David Naylor, Anton Mlikotic, Ilkka Kaitila, Paul Harmatz, Agnes Chen, Patricia Dickson

Research output: Contribution to journalArticle

19 Scopus citations


Background: Intrathecal (IT) enzyme replacement therapy with recombinant human α-L-iduronidase (rhIDU) has been studied to treat glycosaminoglycan storage in the central nervous system of mucopolysaccharidosis (MPS) I dogs and is currently being studied in MPS I patients. Methods: We studied the immune response to IT rhIDU in MPS I subjects with spinal cord compression who had been previously treated with intravenous rhIDU. We measured the concentrations of specific antibodies and cytokines in serum and cerebrospinal fluid (CSF) collected before monthly IT rhIDU infusions and compared the serologic findings with clinical adverse event (AE) reports to establish temporal correlations with clinical symptoms. Results: Five MPS I subjects participating in IT rhIDU trials were studied. One subject with symptomatic spinal cord compression had evidence of an inflammatory response with CSF leukocytosis, elevated interleukin-5, and elevated immunoglobulin G. This subject also complained of lower back pain and buttock paresthesias temporally correlated with serologic abnormalities. Clinical symptoms were managed with oral medication, and serologic abnormalities were resolved, although this subject withdrew from the trial to have spinal decompressive surgery. Conclusion: IT rhIDU was generally well tolerated in the subjects studied, although one subject had moderate to severe clinical symptoms and serologic abnormalities consistent with an immune response.

Original languageEnglish
Pages (from-to)712-720
Number of pages9
JournalPediatric research
Issue number6
StatePublished - Dec 1 2013
Externally publishedYes

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    Vera, M., Le, S., Kan, S. H., Garban, H., Naylor, D., Mlikotic, A., Kaitila, I., Harmatz, P., Chen, A., & Dickson, P. (2013). Immune response to intrathecal enzyme replacement therapy in mucopolysaccharidosis I patients. Pediatric research, 74(6), 712-720.