Enzyme replacement therapy for alpha-mannosidosis: 12 months follow-up of a single centre, randomised, multiple dose study

L. Borgwardt*, C. I. Dali, J. Fogh, J. E. Månsson, K. J. Olsen, H. C. Beck, K. G. Nielsen, L. H. Nielsen, S. O.E. Olsen, H. M.F. Riise Stensland, O. Nilssen, F. Wibrand, A. M. Thuesen, T. Pearl, U. Haugsted, P. Saftig, J. Blanz, S. A. Jones, A. Tylki-Szymanska, N. Guffon-FouilouxM. Beck, A. M. Lund

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Background: Alpha-mannosidosis (OMIM 248500) is a rare lysosomal storage disease (LSD) caused by alpha-mannosidase deficiency. Manifestations include intellectual disabilities, facial characteristics and hearing impairment. A recombinant human alpha-mannosidase (rhLAMAN) has been developed for weekly intravenous enzyme replacement therapy (ERT). We present the preliminary data after 12 months of treatment. Methods: This is a phase I-II study to evaluate safety and efficacy of rhLAMAN. Ten patients (7-17 y) were treated. We investigated efficacy by testing motor function (6-minutes-Walk-Test (6-MWT), 3-min-Stair-Climb-Test (3-MSCT), The Bruininks-Oseretsky Test of Motor Proficiency (BOT2), cognitive function (Leiter-R), oligosaccharides in serum, urine and CSF and Tau- and GFA-protein in CSF. Results: Oligosaccharides: S-, U- and CSF-oligosaccharides decreased 88.6 % (CI -92.0 -85.2, p < 0.001), 54.1 % (CI -69.5- -38.7, p < 0,001), and 25.7 % (CI -44.3- -7.1, p < 0.05), respectively. Biomarkers: CSF-Tau- and GFA-protein decreased 15 %, p < 0.009) and 32.5, p < 0.001 respectively. Motor function: Improvements in 3MSCT (31 steps (CI 6.8-40.5, p < 0.01) and in 6MWT (60.4 m (CI -8.9 -51.1, NS) were achieved. Cognitive function: Improvement in the total Equivalence Age of 4 months (0.34) was achieved in the Leiter R test (CI -0.2-0.8, NS). Conclusions: These data suggest that rhLAMAN may be an encouraging new treatment for patients with alpha-mannosidosis.The study is designed to continue for a total of 18 months. Longer-term follow-up of patients in this study and the future placebo-controlled phase 3 trial are needed to provide greater support for the findings in this study.

Original languageEnglish (US)
Pages (from-to)1015-1024
Number of pages10
JournalJournal of inherited metabolic disease
Volume36
Issue number6
DOIs
StatePublished - Nov 2013

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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