Enzyme replacement therapy for alpha-mannosidosis: 12 months follow-up of a single centre, randomised, multiple dose study
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...
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Published in | Journal of inherited metabolic disease Vol. 36; no. 6; pp. 1015 - 1024 |
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Main Authors | , , , , , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Dordrecht
Springer Netherlands
01.11.2013
Springer Blackwell Publishing Ltd |
Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | Communicated by:Maurizio Scarpa EudraCT number: 2010‐022084‐36 and 2010‐022085‐26 |
ISSN: | 0141-8955 1573-2665 |
DOI: | 10.1007/s10545-013-9595-1 |