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Enzyme replacement therapy for alpha‐mannosidosis: 12 months follow‐up of a single centre, randomised, multiple dose study
Author(s) -
Borgwardt L.,
Dali C. I.,
Fogh J.,
Månsson J. E.,
Olsen K. J.,
Beck H. C.,
Nielsen K. G.,
Nielsen L. H.,
Olsen S. O. E.,
Riise Stensland H. M. F.,
Nilssen O.,
Wibrand F.,
Thuesen A. M.,
Pearl T.,
Haugsted U.,
Saftig P.,
Blanz J.,
Jones S. A.,
TylkiSzymanska A.,
GuffonFouiloux N.,
Beck M.,
Lund A. M.
Publication year - 2013
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/s10545-013-9595-1
Subject(s) - enzyme replacement therapy , medicine , gastroenterology , endocrinology , disease
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.