Inclusion Body Myopathy With Early-Onset Paget Disease And Frontotemporal Dementia

An autosomal dominant disorder characterized by incomplete penetrance of three main features: disabling muscle weakness (in 90%), osteolytic bone lesions consistent with Paget disease (osteitis deformans) (in 51%), and frontotemporal dementia (in 32%). MUSCLE WEAKNESS is an isolated symptom in about 30% of patients and the presenting symptom in greater than half of patients. Mutations in the VCP gene have been identified for IBMPFD1. OMIM: 167320

Also Known As:

Networked: 94 relevant articles (0 outcomes, 7 trials/studies)

Disease Context: Research Results

Related Diseases

1.	Alzheimer Disease (Alzheimer's Disease)
2.	Disease Progression
3.	Muscular Diseases (Myopathy)
4.	Frontotemporal Dementia (Semantic Dementia)
5.	Osteitis Deformans (Paget's Disease of Bone)

Experts

1.	Kimonis, Virginia E: 17 articles (01/2021 - 04/2004)
2.	Weihl, Conrad C: 10 articles (01/2019 - 01/2006)
3.	Kimonis, Virginia: 7 articles (01/2022 - 02/2007)
4.	Nalbandian, Angèle: 6 articles (02/2014 - 10/2010)
5.	Vesa, Jouni: 6 articles (06/2012 - 12/2008)
6.	Watts, Giles D J: 6 articles (03/2008 - 04/2004)
7.	Pestronk, Alan: 5 articles (05/2009 - 04/2004)
8.	Mehta, Sarju G: 5 articles (03/2008 - 04/2004)
9.	Smith, Charles D: 4 articles (01/2021 - 06/2006)
10.	Dec, Eric: 4 articles (02/2014 - 10/2010)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Inclusion Body Myopathy With Early-Onset Paget Disease And Frontotemporal Dementia:

1.	Proteins (Proteins, Gene)FDA Link 06/01/2012 - "Here we utilize two-dimensional difference gel electrophoresis (2D-DIGE) combined with mass spectrometry to study the IBMPFD disorder at the protein level. " 12/14/2009 - "In this study, we find that IBMPFD muscle also accumulates autophagosome-associated proteins, Map1-LC3 (LC3), and p62/sequestosome, which localize to RVs. " 01/01/2023 - "Our findings provide molecular evidence of dysfunctional protein expression in R155H/+ myotubes and offer new therapeutic targets for treating IBMPFD/ALS." 01/01/2018 - "Immunoblotting showed identical total VCP protein levels in human IBMPFD and murine R155C VCP knock-in tissues as compared to wild-type controls. " 01/01/2016 - "Correction: IBMPFD Disease-Causing Mutant VCP/p97 Proteins Are Targets of Autophagic-Lysosomal Degradation."
2.	UbiquitinIBA 12/01/2008 - "Within 20 IBMPFD families whose data was analyzed for this study, ten missense mutations have been identified, the majority of which are located in the N-terminal ubiquitin binding domain. " 02/01/2010 - "We conclude that VCP is essential for maturation of ubiquitin-containing autophagosomes and that defect in this function may contribute to IBMPFD pathogenesis." 02/01/2010 - "VCP/p97 is essential for maturation of ubiquitin-containing autophagosomes and this function is impaired by mutations that cause IBMPFD." 06/01/2006 - "A novel pattern of ubiquitin pathology was identified in IBMPFD that was distinct from sporadic and familial FTLD-U without VCP gene mutations. " 09/01/2005 - "The rare syndrome of IBMPFD (inclusion body myopathy, PDB and fronto-temporal dementia) is due to mutations in the VCP gene and these also cluster in the domain of VCP that interacts with ubiquitin, suggesting a common disease mechanism with SQSTM1-mediated PDB."
3.	Proteasome Endopeptidase Complex (Proteasome)IBA 12/01/2006 - "The rare syndrome of hereditary inclusion body myopathy, PDB, and frontotemporal dementia (IBMPFD) is caused by mutations in the VCP gene, which is involved in regulating I-kappaB degradation by the proteasome. " 10/31/2008 - "The present study shows that IBMPFD mutant expression increases ubiquitinated proteins and susceptibility to proteasome inhibition. " 08/22/2006 - "IBMPFD belongs to a class of genetic diseases associated with an alteration of the ubiquitin-proteasome system." 12/01/2008 - "Inclusion body myopathy (IBM) associated with Paget disease of the bone (PDB) and frontotemporal dementia (FTD) (now called IBMPFD), is a progressive autosomal dominant disorder that was recently identified as being caused by mutations in the VCP (p97 or CDC48) gene which plays a key role in the ubiquitin-proteasome dependent degradation of cytosolic proteins and in the retro translocation of misfolded proteins from the endoplasmic reticulum into the cytoplasm. " 01/01/2021 - "VCP associated inclusion body myopathy, Paget's disease of bone, and Frontotemporal Dementia (IBMPFD, VCP disease, or multisystem proteinopathy type 1 (MSP1)) is an autosomal dominant disease caused by missense mutations in the VCP gene, which plays a crucial role in ubiquitin-proteasome dependent degradation of cytosolic proteins. "
4.	Ubiquitinated ProteinsIBA 06/01/2010 - "The molecular basis underlying impaired degradation and pathological aggregation of ubiquitinated proteins in IBMPFD is unknown. " 04/15/2007 - "We suggest that this early and persistent increase in ubiquitinated proteins induced by IBMPFD mutations in p97/VCP may ultimately lead to animal weakness and the observed muscle pathology. " 10/31/2008 - "The present study shows that IBMPFD mutant expression increases ubiquitinated proteins and susceptibility to proteasome inhibition. " 02/01/2008 - "Biochemically, all IBMPFD VCPs showed elevated ATPase activities as well as elevated binding affinities not only for several VCP cofactors, but also for ubiquitinated proteins. "
5.	Neurofibromin 1 (Neurofibromin)IBA 12/01/2011 - "Certain mutations identified in IBMPFD and NF1 patients reduced the interaction between VCP and neurofibromin and impaired spinogenesis. " 12/01/2011 - "The functions of neurofibromin and VCP in spinogenesis were shown to correlate with the learning disability and dementia phenotypes seen in patients with IBMPFD. " 03/26/2012 - "Although NF1 is recognized as a developmental disorder and IBMPFD is associated with degeneration of multiple tissues, a recent study discovered the direct protein interaction between neurofibromin, the protein product of the NF1 gene, and VCP/p97, encoded by the causative gene of IBMPFD. "
6.	Biomarkers (Surrogate Marker)IBA 01/01/2020 - "Increased Neurofilament Light Chain and YKL-40 CSF Levels in One Japanese IBMPFD Patient With VCP R155C Mutation: A Clinical Case Report With CSF Biomarker Analyses." 01/01/2018 - "We aim to establish a detailed clinical phenotype of VCP disease amongst 35 (28 affected individuals, 7 presymptomatic gene carriers) individuals versus 14 unaffected first-degree relatives in 14 families to establish useful biomarkers for IBMPFD and identify the most meaningful tests for monitoring disease progression in future clinical trials. "
7.	Apolipoproteins E (ApoE)IBA 01/01/2007 - "These data suggest a potential link between APOE 4 genotype and the specific form of frontotemporal dementia found in IBMPFD. " 01/01/2007 - "APOE is a potential modifier gene in an autosomal dominant form of frontotemporal dementia (IBMPFD)." 01/01/2007 - "In this study apolipoprotein-E (APOE) was evaluated for this role in IBMPFD families based on its known modifier effect in Alzheimer's disease. "
8.	ApolipoproteinsIBA 01/01/2007 - "In this study apolipoprotein-E (APOE) was evaluated for this role in IBMPFD families based on its known modifier effect in Alzheimer's disease. "
9.	Valosin Containing ProteinIBA 01/01/2020 - "Valosin-containing protein (VCP) has been identified as the main causative gene of IBMPFD. " 01/01/2013 - "IBMPFD is caused by mutations in the gene that encode valosin-containing protein (VCP). " 08/22/2006 - "Recently, missense mutations in the gene encoding valosin-containing protein (VCP) have been found in individuals with IBMPFD. " 02/15/2006 - "Sequencing of Valosin-containing protein (VCP), the gene associated with IBMPFD, did not identify mutations. " 10/01/2008 - "One form of FTD-U, due to mutations in the valosin containing protein (VCP) gene, occurs with an inclusion body myopathy (IBMPFD). "
10.	ATPases Associated with Diverse Cellular ActivitiesIBA 07/07/2010 - "Mutations in p97, a major cytosolic AAA (ATPases associated with a variety of cellular activities) chaperone, cause inclusion body myopathy associated with Paget's disease of the bone and frontotemporal dementia (IBMPFD). " 01/01/2017 - "The effects caused by these mutations strongly resemble those of pathological mutations of the AAA-ATPase p97 which cause the hereditary proteinopathy IBMPFD (inclusion body myopathy associated with Paget's disease of the bone and frontotemporal dementia). " 11/01/2011 - "IBMPFD is caused by mutations in the ubiquitously expressed valosin-containing protein (VCP) gene, a member of the AAA-ATPase superfamily. " 09/01/2014 - "Mutations in VCP (Valosin-containing protein), an AAA ATPase critical for ER-associated degradation, are linked to IBMPFD (Inclusion body myopathy with Paget disease and frontotemporal dementia). " 02/03/2011 - "Inclusion body myopathy with Paget's disease of bone and frontotemporal dementia (IBMPFD) is caused by mutations in Valosin-containing protein (VCP), a hexameric AAA ATPase that participates in a variety of cellular processes such as protein degradation, organelle biogenesis, and cell-cycle regulation. "

Therapies and Procedures

1.	Therapeutics 06/01/2012 - "In this report, we present data from the first global microarray analyzing IBMPFD patient muscles and elucidating dysregulated pathways to further understand the pathogenesis of the disease and discover potential therapeutics."