Enzyme replacement is associated with better cognitive outcomes after transplant in Hurler syndrome

Abstract

Objective: To investigate whether intravenous enzyme replacement therapy (ERT) benefits cognitive function in patients with mucopolysaccharidosis type IH (Hurler syndrome) undergoing hematopoietic cell transplantation (HCT).

Study design: Data were obtained for 9 children treated with HCT + ERT (ERT group) and 10 children treated with HCT only (no-ERT group) from neuropsychologic evaluations before HCT and at 1-year and 2-year post-HCT follow-up.

Results: At 2 years after HCT, children in the ERT group lost 9.19 fewer IQ points per year compared with children in the no-ERT group (P = .031). Furthermore, the ERT group improved in nonverbal problem solving and processing, whereas the no-ERT group declined, resulting in a difference of 9.44 points per year between the 2 groups (P < .001).

Conclusion: ERT in association with HCT enhances cognitive outcomes, providing new evidence that ERT is a valuable addition to the standard transplantation protocol. Although the mechanism responsible for this improved outcome is unknown, both direct benefits and indirect effects must be considered.

Conflict of interest statement

J.E. has received travel support from Shire Pharmaceuticals. P.O. has received grants for unrelated MPS IH work from Genzyme and has served on the Genzyme speaker’s bureau. CCRF provides financial support to the Blood and Marrow Transplant Service of the University of Minnesota, where P.O. and J.T. are faculty and T.K. is on the clinical service. E.S. has participated on the MPS Registry Board for Genzyme and has received grants from Genzyme, Shire, and Biomarin. C.W. has received grants from Actelion, Amicus, BioMarin, Fairview Hospitals, Genzyme, Pfizer, Protalix, and Shire; has served as a consultant for Actelion, BioMarin, Genzyme, Pfizer, Protalix, and Shire; has been a speaker for Actelion; and owns stock in Zebraic. K.R. and R.Z. declare no conflicts of interest.

Copyright © 2013 Mosby, Inc. All rights reserved.

Figures

Figure 1

Change in cognitive developmental status following HCT.

Figure 2

Change in cognitive developmental status following HCT. Individual trajectories are presented with overall group averages.

Figure 3

Comparison of domains comprising cognitive developmental status 2 years following HCT.