RARE DISEASE
Inclusion body myositis
Inclusion body myositis
Inclusion body myositis
Synonyms: IBM, Sporadic inclusion body myositis, sIBM
Synonyms: IBM, Sporadic inclusion body myositis, sIBM
Synonyms: IBM, Sporadic inclusion body myositis, sIBM
Drug discovery
7
drugs
With orphan designations
Overview
Inclusion Body Myositis (IBM) is a progressive inflammatory myopathy affecting individuals over 50, with a 3:1 male predominance. It causes asymmetric weakness in quadriceps, finger flexors, and swallowing muscles (dysphagia in ~50% of cases). Diagnosis requires clinical assessment, muscle biopsy (inflammatory infiltrates, rimmed vacuoles), and exclusion of mimics. IBM is refractory to immunosuppression and corticosteroids, with management focused on supportive therapies to maintain function [1][6][16].
Burden
Functional decline: 66% require assistive devices (canes, wheelchairs) within 10–15 years [6][15][16].
Healthcare costs: Annual median costs ~$44,838 (vs. $10,182 in controls), driven by rehab and complications [9].
Morbidity: Dysphagia increases aspiration risk; 20% have comorbid autoimmune conditions [5][10][20].
Therapies
Exercise/PT: Key for preserving strength; structured programs improve mobility and reduce falls [3][8][15].
Dysphagia management: Speech therapy and dietary modifications to prevent aspiration [3][6].
No disease-modifying treatments: Corticosteroids/immunosuppressants ineffective; IVIG shows transient benefit in limited cases [1][6][10].
Categories: rare neurological diseases, rare systemic and rheumatological diseases
Research Papers
513 drug discovery papers about Inclusion body myositis, with 3 first-in-class and 4 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
513 drug discovery papers about Inclusion body myositis, with 3 first-in-class and 4 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-08-13 | Sporadic inclusion body myositis: overreliance on histology may lead to misdiagnosis
Abstract We describe a 57-year-old man who had initial isolated weakness in the deep finger flexors of his non-dominant hand, followed by quadriceps weakness and wasting a year later. Despite the distribution specific for sporadic inclusion body myositis (s-IBM) and early myogenic abnormalities found in deep finger flexors, the case was initially misdiagnosed as polymyositis based on the initial biopsy results, which revealed endomysial inflammation with partial invasion/compression of non-necrotic fiber, without rimmed vacuoles. As a result, the patient received unnecessary treatment, including immunosuppressants, which caused serious side effects. The second biopsy revealed rimmed vacuoles, and the diagnosis of s-IBM was confirmed. The role of clinical, pathological, and electrophysiological features for early diagnosis of s-IBM and differentiation from PM is discussed.
2026-07-09 | AAV.hBAG3 Gene Therapy Improves Phenotype in a Valosin Containing Protein Mouse Model of Hereditary Inclusion Body Myositis.
Mutations in the valosin-containing protein (VCP) gene lead to a hereditary type of inclusion body myositis (hIBM), in which sarcoplasmic and myonuclear inclusions with TAR DNA-binding protein 43 (TDP-43) pathology and mitochondrial abnormalities are observed in histological analysis. Pathophysiological conditions in the cell cause the protein quality control system to depend on the autophagy-lysosome pathway (ALP) for degradation of accumulated misfolded proteins and mitochondrial turnover. BCL2-associated athanogene 3 (BAG3) protein has a role in initiating the ALP. Our aim was to ameliorate disease processes resulting from mitochondrial abnormalities and misfolded protein aggregation by upregulating the ALP through overexpression of human BAG3 (hBAG3). The VCP-A232E mouse, a model for hIBM, received AAVrh74.tMCK.hBAG3 systemically at 3 months of age, and outcome measures, including functional, histological, and molecular studies, were assessed 9 months post-gene delivery. hBAG3 treatment improved treadmill running distance and rotarod duration, reduced the number of TDP-43-positive aggregates, and decreased the number of fibers showing abnormalities in mitochondrial enzyme histochemistry, compared with the untreated cohort. Moreover, hBAG3 gene therapy resulted in improvements in mitophagy and mitochondrial homeostasis observed as increased levels in mitophagy markers Parkin and Bnip3, mitochondria biogenesis marker Pgc1α and mitochondrial DNA-encoded subunits of complex IV, Cox1 and Cox3. In addition, the LC-II/I ratio increased, indicating increased autophagic flux. Our study presents evidence that the strategy of supporting the ALP system by overexpressing BAG3 has potential therapeutic use for myodegenerative conditions associated with abnormal protein aggregates and mitochondrial turnover.
2026-06-09 | Phase II/III Study of Ulviprubart in Inclusion Body Myositis: Study Design, Patient Characteristics, and Topline Results (S7.007)
Describe the study design and results of a phase 2/3 study of ulviprubart for treatment of inclusion body myositis (IBM).
2026-06-02 | Genetic Variation in Follistatin and its Role in Muscle Recovery and Hypertrophy: A Dose-Dependent Mechanistic Review
The Follistatin (FST)--Myostatin axis is a primary regulator of skeletalmuscle plasticity, governing both hypertrophy and regenerative capacity. Whilethe anabolic potential of Follistatin overexpression is well-established, thespecific signaling consequences of graded, physiological perturbations (such asthose arising from natural genetic variation or titrated gene therapies) remainunderexplored. This review synthesizes current literature to distinguish betweenthe effects of binary overexpression versus dose-dependent modulation ofFollistatin. We examine the dual mechanisms of FST action: the canonicalsuppression of Smad2/3 signaling via Myostatin/Activin blockade and thecooperative activation of the Akt/mTOR/S6K pathway through obligate IGF-Ireceptor co-signaling. Emerging evidence from human FST polymorphism studiesdemonstrates that naturally occurring variation in the FST locus tonicallymodulates muscle mass and exercise adaptability across the lifespan. Inparallel, phase 1/2a gene therapy trials show that AAV-mediated FST deliveryproduces measurable functional gains in patients with Becker muscular dystrophyand sporadic inclusion body myositis. The same ligand promiscuity that makesFST potent also renders it hazardous in excess: supraphysiological levelssuppress FSH secretion, impair reproductive function, and, through inadvertentGDF11 inhibition, compromise bone integrity. We conclude that future researchmust map the graded dose--response landscape of FST to define the therapeuticwindow for muscle recovery and hypertrophy while avoiding systemic off-targettoxicity.
2026-05-27 | Idiopathic Inflammatory Myopathies-Treatment Perspective of Highly Specialised Rheumatology Centre.
Background/Objectives: Idiopathic inflammatory myopathies (IIMs) are chronic immune-mediated disorders, causing striated muscle weakness and extramuscular symptoms. Real-world, single-centre data are needed to interpret phenotype patterns and evolving therapies. Methods: A single-centre, retrospective cohort study was conducted at the Rheumatology Clinic of the National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland from 1 January 2022 to 31 December 2025. Data included demographics, IIM subtypes, extramuscular involvement, co-existing Sjögren disease (SD), biopsy results, autoantibodies, and treatment. Due to sample size, descriptive analysis was used. Results: The study included 35 patients (31.4% men). Mean age was 50.7 years; mean body mass index (BMI) was 26.0 kg/m2. The cohort consisted of 10 dermatomyositis (DM), one polymyositis (PM), two immune-mediated necrotising myopathy (IMNM), one inclusion body myositis (IBM), 16 anti-synthetase syndrome (ASyS), four juvenile dermatomyositis (JDM), and one clinically amyopathic dermatomyositis (CADM). SD co-occurred in eight cases, including six cases of ASyS. Anti-Jo1 was observed in 13 ASyS cases and one DM. Glucocorticoids (GCSs) were administered in all patients for induction in addition to cyclophosphamide (28.6%), mycophenolate mofetil (MMF) (51.4%), and methotrexate (MTX) (17.1%). Maintenance therapy included MTX (20%), MMF (31.4%), rituximab (34.3%), azathioprine (AZA) (42.9%), and others. Two DM, two JDM, and one ASyS patient received JAK inhibitors, one DM and one JDM anifrolumab, one IBM sirolimus, and four patients with interstitial lung disease (ILD) nintedanib. Conclusions: This Polish single-centre cohort shows effective use of novel therapies for IIM. Sirolimus, JAK inhibitors, and nintedanib were effective. Co-occurrence of SD in ASyS patients requires further research.
2026-08-13 | Sporadic inclusion body myositis: overreliance on histology may lead to misdiagnosis
Abstract We describe a 57-year-old man who had initial isolated weakness in the deep finger flexors of his non-dominant hand, followed by quadriceps weakness and wasting a year later. Despite the distribution specific for sporadic inclusion body myositis (s-IBM) and early myogenic abnormalities found in deep finger flexors, the case was initially misdiagnosed as polymyositis based on the initial biopsy results, which revealed endomysial inflammation with partial invasion/compression of non-necrotic fiber, without rimmed vacuoles. As a result, the patient received unnecessary treatment, including immunosuppressants, which caused serious side effects. The second biopsy revealed rimmed vacuoles, and the diagnosis of s-IBM was confirmed. The role of clinical, pathological, and electrophysiological features for early diagnosis of s-IBM and differentiation from PM is discussed.
2026-07-09 | AAV.hBAG3 Gene Therapy Improves Phenotype in a Valosin Containing Protein Mouse Model of Hereditary Inclusion Body Myositis.
Mutations in the valosin-containing protein (VCP) gene lead to a hereditary type of inclusion body myositis (hIBM), in which sarcoplasmic and myonuclear inclusions with TAR DNA-binding protein 43 (TDP-43) pathology and mitochondrial abnormalities are observed in histological analysis. Pathophysiological conditions in the cell cause the protein quality control system to depend on the autophagy-lysosome pathway (ALP) for degradation of accumulated misfolded proteins and mitochondrial turnover. BCL2-associated athanogene 3 (BAG3) protein has a role in initiating the ALP. Our aim was to ameliorate disease processes resulting from mitochondrial abnormalities and misfolded protein aggregation by upregulating the ALP through overexpression of human BAG3 (hBAG3). The VCP-A232E mouse, a model for hIBM, received AAVrh74.tMCK.hBAG3 systemically at 3 months of age, and outcome measures, including functional, histological, and molecular studies, were assessed 9 months post-gene delivery. hBAG3 treatment improved treadmill running distance and rotarod duration, reduced the number of TDP-43-positive aggregates, and decreased the number of fibers showing abnormalities in mitochondrial enzyme histochemistry, compared with the untreated cohort. Moreover, hBAG3 gene therapy resulted in improvements in mitophagy and mitochondrial homeostasis observed as increased levels in mitophagy markers Parkin and Bnip3, mitochondria biogenesis marker Pgc1α and mitochondrial DNA-encoded subunits of complex IV, Cox1 and Cox3. In addition, the LC-II/I ratio increased, indicating increased autophagic flux. Our study presents evidence that the strategy of supporting the ALP system by overexpressing BAG3 has potential therapeutic use for myodegenerative conditions associated with abnormal protein aggregates and mitochondrial turnover.
2026-06-09 | Phase II/III Study of Ulviprubart in Inclusion Body Myositis: Study Design, Patient Characteristics, and Topline Results (S7.007)
Describe the study design and results of a phase 2/3 study of ulviprubart for treatment of inclusion body myositis (IBM).
2026-06-02 | Genetic Variation in Follistatin and its Role in Muscle Recovery and Hypertrophy: A Dose-Dependent Mechanistic Review
The Follistatin (FST)--Myostatin axis is a primary regulator of skeletalmuscle plasticity, governing both hypertrophy and regenerative capacity. Whilethe anabolic potential of Follistatin overexpression is well-established, thespecific signaling consequences of graded, physiological perturbations (such asthose arising from natural genetic variation or titrated gene therapies) remainunderexplored. This review synthesizes current literature to distinguish betweenthe effects of binary overexpression versus dose-dependent modulation ofFollistatin. We examine the dual mechanisms of FST action: the canonicalsuppression of Smad2/3 signaling via Myostatin/Activin blockade and thecooperative activation of the Akt/mTOR/S6K pathway through obligate IGF-Ireceptor co-signaling. Emerging evidence from human FST polymorphism studiesdemonstrates that naturally occurring variation in the FST locus tonicallymodulates muscle mass and exercise adaptability across the lifespan. Inparallel, phase 1/2a gene therapy trials show that AAV-mediated FST deliveryproduces measurable functional gains in patients with Becker muscular dystrophyand sporadic inclusion body myositis. The same ligand promiscuity that makesFST potent also renders it hazardous in excess: supraphysiological levelssuppress FSH secretion, impair reproductive function, and, through inadvertentGDF11 inhibition, compromise bone integrity. We conclude that future researchmust map the graded dose--response landscape of FST to define the therapeuticwindow for muscle recovery and hypertrophy while avoiding systemic off-targettoxicity.
2026-05-27 | Idiopathic Inflammatory Myopathies-Treatment Perspective of Highly Specialised Rheumatology Centre.
Background/Objectives: Idiopathic inflammatory myopathies (IIMs) are chronic immune-mediated disorders, causing striated muscle weakness and extramuscular symptoms. Real-world, single-centre data are needed to interpret phenotype patterns and evolving therapies. Methods: A single-centre, retrospective cohort study was conducted at the Rheumatology Clinic of the National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland from 1 January 2022 to 31 December 2025. Data included demographics, IIM subtypes, extramuscular involvement, co-existing Sjögren disease (SD), biopsy results, autoantibodies, and treatment. Due to sample size, descriptive analysis was used. Results: The study included 35 patients (31.4% men). Mean age was 50.7 years; mean body mass index (BMI) was 26.0 kg/m2. The cohort consisted of 10 dermatomyositis (DM), one polymyositis (PM), two immune-mediated necrotising myopathy (IMNM), one inclusion body myositis (IBM), 16 anti-synthetase syndrome (ASyS), four juvenile dermatomyositis (JDM), and one clinically amyopathic dermatomyositis (CADM). SD co-occurred in eight cases, including six cases of ASyS. Anti-Jo1 was observed in 13 ASyS cases and one DM. Glucocorticoids (GCSs) were administered in all patients for induction in addition to cyclophosphamide (28.6%), mycophenolate mofetil (MMF) (51.4%), and methotrexate (MTX) (17.1%). Maintenance therapy included MTX (20%), MMF (31.4%), rituximab (34.3%), azathioprine (AZA) (42.9%), and others. Two DM, two JDM, and one ASyS patient received JAK inhibitors, one DM and one JDM anifrolumab, one IBM sirolimus, and four patients with interstitial lung disease (ILD) nintedanib. Conclusions: This Polish single-centre cohort shows effective use of novel therapies for IIM. Sirolimus, JAK inhibitors, and nintedanib were effective. Co-occurrence of SD in ASyS patients requires further research.
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Drug Discovery Landscape
7 orphan drug designations for Inclusion body myositis.
7 orphan drug designations for Inclusion body myositis.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Ulviprubart | antibodies | EMA | 2023-07-25 | — | PHARA |
Humanized afucosylated IgG1 monoclonal antibody binding to KLRG1 | antibodies | FDA | 2020-07-07 | — | Abcuro, Inc. |
arimoclomol | small molecules | FDA | 2017-11-02 | — | KemPharm Denmark A/S |
Adeno-associated virus delivered transgene of follistatin | gene therapies | FDA | 2016-09-19 | — | Milo Biotechnology |
Arimoclomol citrate [Miplyffa] | small molecules | EMA | 2016-05-30 | — | Orphazyme A/S |
Bimagrumab | antibodies | EMA | 2012-08-09 | — | Novartis Europharm Limited |
bimagrumab | antibodies | FDA | 2012-06-18 | — | Novartis Pharmaceuticals Corp. |
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