.

Research News

Site presented by Bill Tillier.

2017

Amici, D. R., Pinal-Fernandez, I., Mázala, D. A. G., Lloyd, T. E., Corse, A. M., Christopher-Stine, L., et al. (2017). Calcium dysregulation, functional calpainopathy, and endoplasmic reticulum stress in sporadic inclusion body myositis. Acta Neuropathologica Communications, 5(1), 24. http://doi.org/10.1186/s40478-017-0427-7

Gallay L, Petiot P. Sporadic inclusion-body myositis: Recent advances and the state of the art in 2016. Revue neurologique (2016), http://dx.doi.org/10.1016/j.neurol.2016.07.016
abstract: Sporadic inclusion-body myositis (sIBM) is the most frequent myopathy after 50 years of age. As the clinical presentation may often be typical, pathological confirmation by muscle biopsy may be necessary, but sometimes difficult. Further delineation of the framework of this particular disease, especially during its early-onset stage, appears to be challenging. New classifications of diagnostic criteria as well as the identification of new diagnostic hallmarks appear to be the two main tools towards achieving this purpose. sIBM pathophysiology has long been discussed and yet remains controversial. Since its initial description, there have been two major pathogenic hypotheses: inflammatory and degenerative. To date, the debate is still ongoing, as recent works support both these pathophysiological mechanisms, although the inflammatory process seems to be slightly more preeminent in the recent literature. Treatment remains the most disappointing aspect of the disease as, despite various therapeutic attempts, no significant efficacy has been reported thus far. Nevertheless, advances in our pathophysiological understanding of the disease are paving the way for further therapeutic perspectives that might arise in the years to come. The objective of the present work was to summarize the most significant data published on sIBM during the past 2 years.
At present, our understanding and management of sIBM appears to be at a crossroads. Significant advances have been made, but more have yet to be achieved in this complex disease. New insights into its pathogenic processes could serve as rationales for future therapeutic perspectives for this unresponsive disease. A more permissive classification would also be useful for allowing the diagnosis to be made early in the onset of the disease, a stage at which treatment could potentially be more effective.

Meyer, A., Lannes, B., Goetz, J., Echaniz-Laguna, A., Lipsker, D., Arnaud, L., . . Sibilia, J. (2017). Inflammatory muscle disease: A new landscape. Joint Bone Spine. http://doi.org/10.1016/j.jbspin.2017.03.005
-In the past, IBM has been notoriously misdiagnosed usually first as polymyositis
-Again, in the past, polymyositis was perceived as a fairly common disorder
-This new study states the following: polymyositis is now emerging as a rare entity that is often mistaken for more recently described patterns of IMD [inflammatory muscle diseases].

Greenberg, S. A. (2017). Inclusion Body Myositis Pathogenesis: Steady Progress. Annals of Neurology. http://doi.org/10.1002/ana.24920

Tawara, N., Yamashita, S., Zhang, X., Korogi, M., Zhang, Z., Doki, T., . . . Ando, Y. (2017). Pathomechanisms of anti-cN1A autoantibodies in sporadic inclusion body myositis. Annals of Neurology. http://doi.org/10.1002/ana.24919

Cerino, M., Gorokhova, S., Laforet, P., Ben Yaou, R., Salort-Campana, E., Pouget, J., . . . Krahn, M. (2017). Genetic characterization of a French cohort of GNE-mutation negative inclusion body myopathy patients using exome sequencing. Muscle & Nerve, 4(2012), 2-14. http://doi.orTawara, N., Yamashita, S., Zhang, X., Korogi, M., Zhang, Z., Doki, T., … Ando, Y. (2017). Pathomechanisms of anti-cN1A autoantibodies in sporadic inclusion body myositis. Annals of Neurology. http://doi.org/10.1002/ana.24919 g/10.1002/mus.25638

Johari, M., Arumilli, M., Palmio, J., Savarese, M., Tasca, G., Mirabella, M., . . . Udd, B. (2017). Association study reveals novel risk loci for sporadic inclusion body myositis. European Journal of Neurology, 24(4), 572-577. http://doi.org/10.1111/ene.13244

Mendell, J. R., Sahenk, Z., Al-zaidy, S., Rodino-klapac, L. R., Lowes, P., Alfano, L., . . . Brian, K. (2017). Follistatin Gene Therapy for Sporadic Inclusion Body Myositis Improves Functional Outcomes. Molecular Therapy, 25(4), 1-10. http://doi.org/10.1016/j.ymthe.2017.02.015

Rothwell, S., Cooper, R. G., Lundberg, I. E., Gregersen, P. K., Hanna, M. G., Machado, P. M., . . . Chinoy, H. (2017). Immune-array Analysis in Sporadic Inclusion Body Myositis Reveals HLA-DRB1 Amino Acid Heterogeneity across the Myositis Spectrum. Arthritis & Rheumatology, 11(10), 300-308. http://doi.org/10.1002/art.40045

McHugh, J. (2017). Inflammatory myopathies: Genetic associations with IBM. Nature Reviews Rheumatology, 2017. http://doi.org/10.1038/nrrheum.2017.8 available here

The HLA region is strongly associated with inclusion body myositis (IBM), according to new findings published in Arthritis & Rheumatology, confirming an immune-related genetic component in this subtype of myositis. “While a degenerative component is recognised [in IBM], this is the first study to focus solely on immune-related genes,” comments corresponding author Simon Rothwell. “Since there is no proven treatment in IBM, the identification of new genetic risk factors may ultimately lead to new effective treatments.”
A report by McHugh on Rothwell, S., Cooper, R. G., Lundberg, I. E., Gregersen, P. K., Hanna, M. G., Machado, P. M., . . . Chinoy, H. (2017). Immune-array Analysis in Sporadic Inclusion Body Myositis Reveals HLA-DRB1 Amino Acid Heterogeneity across the Myositis Spectrum. Arthritis & Rheumatology, 11(10), 300-308. http://doi.org/10.1002/art.40045
McHugh, J. (2017). Inflammatory myopathies: Genetic associations with IBM. Nat Rev Rheumatol

Rare variants in SQSTM1 and VCP genes
Gang, Q., Bettencourt, C., Machado, P. M., Brady, S., Holton, J. L., Pittman, A. M., . . . Houlden, H. (2016). Rare variants in SQSTM1 and VCP genes and risk of sporadic inclusion body myositis. Neurobiology of Aging, 47, 218.e1-218.e9. http://doi.org/10.1016/j.neurobiolaging.2016.07.024

Proteomics of rimmed vacuoles
Guttsches, A., Brady, S., Krause, K., Maerkens, A., Uszkoreit, J., Eisenacher, M., . . . Kley, R. A. (2016). Proteomics of rimmed vacuoles define new risk allele in inclusion body myositis. Annals of Neurology. http://doi.org/10.1002/ana.24847

autoantibody profile and clinical characteristics
Lilleker, J. B., Rietveld, A., Pye, S. R., Mariampillai, K., Benveniste, O., Peeters, M. T. J., . . . van Engelen, B. G. M. (2017). Cytosolic 5'-nucleotidase 1A autoantibody profile and clinical characteristics in inclusion body myositis. Annals of the Rheumatic Diseases, annrheumdis-2016-210282. http://doi.org/10.1136/annrheumdis-2016-210282

The role of p62/SQSTM1
Nakano, S., Oki, M., & Kusaka, H. (2016). The role of p62/SQSTM1 in sporadic inclusion body myositis. Neuromuscular Disorders. http://doi.org/10.1016/j.nmd.2016.12.009

A myodegenerative disease or an inflammatory myopathy
Weihl, C. C., & Mammen, A. L. (2017). Sporadic Inclusion Body Myositis: A myodegenerative disease or an inflammatory myopathy. Neuropathology and Applied Neurobiology, 38(1), 42-49. http://doi.org/10.1111/nan.12384