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Intravenous immune globulin in hereditary inclusion body myopathy: a pilot study

BACKGROUND: Hereditary Inclusion Body Myopathy (HIBM) is an autosomal recessive, adult onset, non-inflammatory neuromuscular disorder with no effective treatment. The causative gene, GNE, codes for UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase, which catalyzes the first two reaction...

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Autores principales: Sparks, Susan, Rakocevic, Goran, Joe, Galen, Manoli, Irini, Shrader, Joseph, Harris-Love, Michael, Sonies, Barbara, Ciccone, Carla, Dorward, Heidi, Krasnewich, Donna, Huizing, Marjan, Dalakas, Marinos C, Gahl, William A
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1790898/
https://www.ncbi.nlm.nih.gov/pubmed/17261181
http://dx.doi.org/10.1186/1471-2377-7-3
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author Sparks, Susan
Rakocevic, Goran
Joe, Galen
Manoli, Irini
Shrader, Joseph
Harris-Love, Michael
Sonies, Barbara
Ciccone, Carla
Dorward, Heidi
Krasnewich, Donna
Huizing, Marjan
Dalakas, Marinos C
Gahl, William A
author_facet Sparks, Susan
Rakocevic, Goran
Joe, Galen
Manoli, Irini
Shrader, Joseph
Harris-Love, Michael
Sonies, Barbara
Ciccone, Carla
Dorward, Heidi
Krasnewich, Donna
Huizing, Marjan
Dalakas, Marinos C
Gahl, William A
author_sort Sparks, Susan
collection PubMed
description BACKGROUND: Hereditary Inclusion Body Myopathy (HIBM) is an autosomal recessive, adult onset, non-inflammatory neuromuscular disorder with no effective treatment. The causative gene, GNE, codes for UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase, which catalyzes the first two reactions in the synthesis of sialic acid. Reduced sialylation of muscle glycoproteins, such as α-dystroglycan and neural cell adhesion molecule (NCAM), has been reported in HIBM. METHODS: We treated 4 HIBM patients with intravenous immune globulin (IVIG), in order to provide sialic acid, because IgG contains 8 μmol of sialic acid/g. IVIG was infused as a loading dose of 1 g/kg on two consecutive days followed by 3 doses of 400 mg/kg at weekly intervals. RESULTS: For all four patients, mean quadriceps strength improved from 19.0 kg at baseline to 23.2 kg (+22%) directly after IVIG loading to 25.6 kg (+35%) at the end of the study. Mean shoulder strength improved from 4.1 kg at baseline to 5.9 kg (+44%) directly after IVIG loading to 6.0 kg (+46%) at the end of the study. The composite improvement for 8 other muscle groups was 5% after the initial loading and 19% by the end of the study. Esophageal motility and lingual strength improved in the patients with abnormal barium swallows. Objective measures of functional improvement gave variable results, but the patients experienced improvements in daily activities that they considered clinically significant. Immunohistochemical staining and immunoblotting of muscle biopsies for α-dystroglycan and NCAM did not provide consistent evidence for increased sialylation after IVIG treatment. Side effects were limited to transient headaches and vomiting. CONCLUSION: The mild benefits in muscle strength experienced by HIBM patients after IVIG treatment may be related to the provision of sialic acid supplied by IVIG. Other sources of sialic acid are being explored as treatment options for HIBM.
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spelling pubmed-17908982007-02-03 Intravenous immune globulin in hereditary inclusion body myopathy: a pilot study Sparks, Susan Rakocevic, Goran Joe, Galen Manoli, Irini Shrader, Joseph Harris-Love, Michael Sonies, Barbara Ciccone, Carla Dorward, Heidi Krasnewich, Donna Huizing, Marjan Dalakas, Marinos C Gahl, William A BMC Neurol Research Article BACKGROUND: Hereditary Inclusion Body Myopathy (HIBM) is an autosomal recessive, adult onset, non-inflammatory neuromuscular disorder with no effective treatment. The causative gene, GNE, codes for UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase, which catalyzes the first two reactions in the synthesis of sialic acid. Reduced sialylation of muscle glycoproteins, such as α-dystroglycan and neural cell adhesion molecule (NCAM), has been reported in HIBM. METHODS: We treated 4 HIBM patients with intravenous immune globulin (IVIG), in order to provide sialic acid, because IgG contains 8 μmol of sialic acid/g. IVIG was infused as a loading dose of 1 g/kg on two consecutive days followed by 3 doses of 400 mg/kg at weekly intervals. RESULTS: For all four patients, mean quadriceps strength improved from 19.0 kg at baseline to 23.2 kg (+22%) directly after IVIG loading to 25.6 kg (+35%) at the end of the study. Mean shoulder strength improved from 4.1 kg at baseline to 5.9 kg (+44%) directly after IVIG loading to 6.0 kg (+46%) at the end of the study. The composite improvement for 8 other muscle groups was 5% after the initial loading and 19% by the end of the study. Esophageal motility and lingual strength improved in the patients with abnormal barium swallows. Objective measures of functional improvement gave variable results, but the patients experienced improvements in daily activities that they considered clinically significant. Immunohistochemical staining and immunoblotting of muscle biopsies for α-dystroglycan and NCAM did not provide consistent evidence for increased sialylation after IVIG treatment. Side effects were limited to transient headaches and vomiting. CONCLUSION: The mild benefits in muscle strength experienced by HIBM patients after IVIG treatment may be related to the provision of sialic acid supplied by IVIG. Other sources of sialic acid are being explored as treatment options for HIBM. BioMed Central 2007-01-29 /pmc/articles/PMC1790898/ /pubmed/17261181 http://dx.doi.org/10.1186/1471-2377-7-3 Text en Copyright © 2007 Sparks et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Sparks, Susan
Rakocevic, Goran
Joe, Galen
Manoli, Irini
Shrader, Joseph
Harris-Love, Michael
Sonies, Barbara
Ciccone, Carla
Dorward, Heidi
Krasnewich, Donna
Huizing, Marjan
Dalakas, Marinos C
Gahl, William A
Intravenous immune globulin in hereditary inclusion body myopathy: a pilot study
title Intravenous immune globulin in hereditary inclusion body myopathy: a pilot study
title_full Intravenous immune globulin in hereditary inclusion body myopathy: a pilot study
title_fullStr Intravenous immune globulin in hereditary inclusion body myopathy: a pilot study
title_full_unstemmed Intravenous immune globulin in hereditary inclusion body myopathy: a pilot study
title_short Intravenous immune globulin in hereditary inclusion body myopathy: a pilot study
title_sort intravenous immune globulin in hereditary inclusion body myopathy: a pilot study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1790898/
https://www.ncbi.nlm.nih.gov/pubmed/17261181
http://dx.doi.org/10.1186/1471-2377-7-3
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