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Review
. 2023 Mar;270(3):1787-1797.
doi: 10.1007/s00415-022-11459-3. Epub 2022 Nov 18.

Inclusion body myositis: from genetics to clinical trials

Sara Nagy  1   2 , Alaa Khan  3   4 , Pedro M Machado  5   6 , Henry Houlden  3
Affiliations
Review

Inclusion body myositis: from genetics to clinical trials

Sara Nagy et al. J Neurol. 2023 Mar.

Abstract

Inclusion body myositis (IBM) belongs to the group of idiopathic inflammatory myopathies and is characterized by a slowly progressive disease course with asymmetric muscle weakness of predominantly the finger flexors and knee extensors. The disease leads to severe disability and most patients lose ambulation due to lack of curative or disease-modifying treatment options. Despite some genes reported to be associated with hereditary IBM (a distinct group of conditions), data on the genetic susceptibility of sporadic IBM are very limited. This review gives an overview of the disease and focuses on the current genetic knowledge and potential therapeutic implications.

Keywords: Clinical trials; Gene therapy; Genetic susceptibility; Hereditary inclusion body myositis; Inflammation; Neurodegeneration; Sporadic inclusion body myositis.

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Conflict of interest statement

PMM has received honoraria from Abbvie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB. The other authors have no conflict of interest related to this publication.

Figures

Fig. 1
Fig. 1
IBM diagnostic workup and improved (more sensitive and specific) classification criteria with *future inclusion of testing for genetic susceptibility
Fig. 2
Fig. 2
Schematic representation of IBM disease pathomechanism including inflammatory, degenerative, and mitochondrial pathways, and including the role of genetic susceptibility in every underlying mechanism
Fig. 3
Fig. 3
(A) Manhattan plot from immune SNP-genotyping based association analysis showing MHC region as the most strongly associated region in sIBM, adapted from [18]. (B) Manhattan plot generated from exome-sequencing based association analysis (unpublished data)
See this image and copyright information in PMC

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