Intravenous immune globulin in hereditary inclusion body myopathy: a pilot study
Susan Sparks1 ,2, Goran Rakocevic3, Galen Joe4, Irini Manoli1, Joseph Shrader4, Michael Harris-Love4 ,5, Barbara Sonies6, Carla Ciccone1, Heidi Dorward1, Donna Krasnewich1, Marjan Huizing1, Marinos C Dalakas3 and William A Gahl1
1Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
2Department of Genetics and Metabolism, Children's National Medical Center, Washington DC, USA
3Neuromuscular Diseases Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA
4Department of Rehabilitation Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA
5George Washington University School of Medicine and Health Sciences, Washington DC, USA
6University of Maryland, Department of Hearing and Speech Sciences, College Park, MD, USA
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.
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.
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.
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.
BMC Neurology 2007, 7:3. This is an Open Access article distributed under the terms of the Creative Commons Attribution License.