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

Line Gutte Borgwardt; Christine I. Dali; J Fogh; Joan Månsson; K J Olsen; Hans Christian Beck; K G Nielsen; L H Nielsen; S O E Olsen; H M F Riise Stensland; O Nilssen; F Wibrand; Anne-Marie Thuesen; T Pearl; U Haugsted; P Saftig; J Blanz; Sheila Jones; A Tylki-Szymanska; N Guffon-Fouiloux; Marie Valentin Beck; A M Lund

doi:10.1007/s10545-013-9595-1

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

Line Gutte Borgwardt, Christine I. Dali, J Fogh, Joan Månsson, K J Olsen, Hans Christian Beck, K G Nielsen, L H Nielsen, S O E Olsen, H M F Riise Stensland, O Nilssen, F Wibrand, Anne-Marie Thuesen, T Pearl, U Haugsted, P Saftig, J Blanz, Sheila Jones, A Tylki-Szymanska, N Guffon-FouilouxMarie Valentin Beck, A M Lund

27 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	Journal of Inherited Metabolic Disease
Vol/bind	36
Udgave nummer	6
Sider (fra-til)	1015-1024
Antal sider	10
ISSN	0141-8955
DOI	https://doi.org/10.1007/s10545-013-9595-1
Status	Udgivet - nov. 2013

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10.1007/s10545-013-9595-1

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Borgwardt, L. G., Dali, C. I., Fogh, J., Månsson, J., 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., Tylki-Szymanska, A., ... Lund, A. M. (2013). Enzyme replacement therapy for alpha-mannosidosis: 12 months follow-up of a single centre, randomised, multiple dose study. Journal of Inherited Metabolic Disease, 36(6), 1015-1024. https://doi.org/10.1007/s10545-013-9595-1

Borgwardt, LG, Dali, CI, Fogh, J, Månsson, J, Olsen, KJ, Beck, HC, Nielsen, KG, Nielsen, LH, Olsen, SOE, Riise Stensland, HMF, Nilssen, O, Wibrand, F, Thuesen, A-M, Pearl, T, Haugsted, U, Saftig, P, Blanz, J, Jones, S, Tylki-Szymanska, A, Guffon-Fouiloux, N, Beck, MV & Lund, AM 2013, 'Enzyme replacement therapy for alpha-mannosidosis: 12 months follow-up of a single centre, randomised, multiple dose study', Journal of Inherited Metabolic Disease, bind 36, nr. 6, s. 1015-1024. https://doi.org/10.1007/s10545-013-9595-1

@article{19034174b6544b9f8ea1ca8395f82dd6,

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

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.",

author = "Borgwardt, {Line Gutte} and Dali, {Christine I.} and J Fogh and Joan M{\aa}nsson and Olsen, {K J} and Beck, {Hans Christian} and Nielsen, {K G} and Nielsen, {L H} and Olsen, {S O E} and {Riise Stensland}, {H M F} and O Nilssen and F Wibrand and Anne-Marie Thuesen and T Pearl and U Haugsted and P Saftig and J Blanz and Sheila Jones and A Tylki-Szymanska and N Guffon-Fouiloux and Beck, {Marie Valentin} and Lund, {A M}",

year = "2013",

month = nov,

doi = "10.1007/s10545-013-9595-1",

language = "English",

volume = "36",

pages = "1015--1024",

journal = "Journal of Inherited Metabolic Disease",

issn = "0141-8955",

publisher = "Springer",

number = "6",

}

TY - JOUR

T1 - Enzyme replacement therapy for alpha-mannosidosis

T2 - 12 months follow-up of a single centre, randomised, multiple dose study

AU - Borgwardt, Line Gutte

AU - Dali, Christine I.

AU - Fogh, J

AU - Månsson, Joan

AU - Olsen, K J

AU - Beck, Hans Christian

AU - Nielsen, K G

AU - Nielsen, L H

AU - Olsen, S O E

AU - Riise Stensland, H M F

AU - Nilssen, O

AU - Wibrand, F

AU - Thuesen, Anne-Marie

AU - Pearl, T

AU - Haugsted, U

AU - Saftig, P

AU - Blanz, J

AU - Jones, Sheila

AU - Tylki-Szymanska, A

AU - Guffon-Fouiloux, N

AU - Beck, Marie Valentin

AU - Lund, A M

PY - 2013/11

Y1 - 2013/11

N2 - 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.

AB - 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.

U2 - 10.1007/s10545-013-9595-1

DO - 10.1007/s10545-013-9595-1

M3 - Journal article

C2 - 23494656

SN - 0141-8955

VL - 36

SP - 1015

EP - 1024

JO - Journal of Inherited Metabolic Disease

JF - Journal of Inherited Metabolic Disease

IS - 6

ER -

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

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