Intrathecal enzyme replacement for cognitive decline in mucopolysaccharidosis type I, a randomized, open-label, controlled pilot study.

Abstract

Central nervous system manifestations of mucopolysaccharidosis type I (MPS I) such as cognitive impairment, hydrocephalus, and spinal cord compression are inadequately treated by intravenously-administered enzyme replacement therapy with laronidase (recombinant human alpha-L-iduronidase). While hematopoietic stem cell transplantation treats neurological symptoms, this therapy is not generally offered to attenuated MPS I patients. This study is a randomized, open-label, controlled pilot study of intrathecal laronidase in eight attenuated MPS I patients with cognitive impairment. Subjects ranged between 12 years and 50 years old with a median age of 18 years. All subjects had received intravenous laronidase prior to the study over a range of 4 to 10 years, with a mean of 7.75 years. Weekly intravenous laronidase was continued throughout the duration of the study. The randomization period was one year, during which control subjects attended all study visits and assessments, but did not receive any intrathecal laronidase. After the first year, all eight subjects received treatment for one additional year. There was no significant difference in neuropsychological assessment scores between control or treatment groups, either over the one-year randomized period or at 18 or 24 months. However, there was no significant decline in scores in the control group either. Adverse events included pain (injection site, back, groin), headache, neck spasm, and transient blurry vision. There were seven serious adverse events, one judged as possibly related (headache requiring hospitalization). There was no significant effect of intrathecal laronidase on cognitive impairment in older, attenuated MPS I patients over a two-year treatment period. A five-year open-label extension study is underway.

• Authors: Agnes H Chen, Paul Harmatz, Igor Nestrasil, Julie B Eisengart, Kelly E King, Kyle Rudser, Alexander M Kaizer, Alena Svatkova, Amy Wakumoto, Steven Q Le, Jacqueline Madden, Sarah Young, Haoyue Zhang, Lynda E Polgreen, Patricia I Dickson
• Journal: Molecular genetics and metabolism (Mol Genet Metab) Vol. 129 Issue 2 Pg. 80-90 (02 2020) ISSN: 1096-7206 [Electronic] United States
• PMID: 31839529 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Recombinant Proteins
• Iduronidase

Topics

• Adolescent
• Adult
• Child
• Cognitive Dysfunction (drug therapy, etiology)
• Enzyme Replacement Therapy (adverse effects, methods)
• Female
• Humans
• Iduronidase (adverse effects, therapeutic use)
• Injections, Spinal
• Male
• Middle Aged
• Mucopolysaccharidosis I (complications)
• Pilot Projects
• Prospective Studies
• Recombinant Proteins (adverse effects, therapeutic use)
• Research Design
• Young Adult