VCP evolved very early in the development of animal life forms.  The following chart (excerpted from a paper below) illustrates the many functions of VCP; thus, the difficulty in finding treatments for IBMPFD, but the importance of understanding VCP for a variety of other medical effects, e.g., other diseases, aging, some cancers.

 

The following are references that can be accessed by clicking on the associated link (i.e., the title):

IBM can mean either "Inclusion Body Myopathy" or "Inclusion Body Myocitis".  Some of the aspects of these various diseases are listed in this chart.

The report from the first IBMPFD conference in 2015 summarizes the current state of knowledge: ENMC Workshop.

This is the ENMC Impact Report for 2015, which includes a reference to the Workshop and VCP Disease.

Inclusion Body Myopathy - Paget Bone Disease - Frontotemporal Dementia Syndrome Caused by Mutated Valosin Containing Protein.

Giles D. J. Watts1, Jill Wymer1, Margaret J. Kovach2, Sarju G. Mehta1, Steven Mumm3, Daniel Darvish4, Alan Pestronk5, Michael P. Whyte3, Virginia E. Kimonis1.

1 Division of Genetics, Children's Hospital Boston, Harvard Medical School, Boston, MA, USA 2 University of Tennessee at Chattanooga, Department of Biological and Environmental Sciences, 215 Holt Hall-Department 2653, Chattanooga, TN

3 Division of Bone and Mineral Diseases, Washington University School of Medicine at Barnes-Jewish Hospital; and Center for Metabolic Bone Disease and Molecular Research, Shriners Hospitals for Children, St. Louis, MO, USA (SM, MPW) 4 HIBM Research Group, 16661 Ventura Blvd., #311, Encino, CA, USA 5 Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA

Pathological consequences of VCP mutations on human striated muscle

Christian U. Hubbers,1, Christoph S. Clemen,1,2, Kristina Kesper,3 Annett Bo¨ ddrich,7 Andreas Hofmann,9 Outi Ka¨ma¨ra¨inen,9 Karen Tolksdorf,3 Maria Stumpf,1 Julia Reichelt,1 Udo Roth,2 Sabine Krause,8 Giles Watts,10 Virginia Kimonis,10 Mike P. Wattjes,4 Jens Reimann,3 Dietmar R. Thal,5 Katharina Biermann,6 Bernd O. Evert,3 Hanns Lochmüller,8 Erich E. Wanker,7 Benedikt G. H. Schoser,8 Angelika A. Noegel1,2 and Rolf Schroder1

1Institute of Biochemistry I, 2Center for Molecular Medicine Cologne, Medical Faculty, University of Cologne, Cologne, 3Department of Neurology, 4Department of Radiology, 5Institute for Neuropathology, 6Institute of Pathology, University Hospital Bonn, Bonn, 7Department of Neuroproteomics, Max Delbrück Center for Molecular Medicine, Berlin, 8Friedrich-Baur-Institut and Department of Neurology, Ludwig Maximilians University of Munich, München, Germany, 9Institute of Structural and Molecular Biology, School of Biological Sciences, The University of Edinburgh, Edinburgh, UK and 10Division of Genetics, Children’s Hospital Boston, Harvard Medical School, Boston, MA, USA

Inclusion body myopathy-associated mutations in p97/VCP impair endoplasmic reticulum-associated degradation

Conrad C. Weihl1,2,*, Seema Dalal2, Alan Pestronk1 and Phyllis I. Hanson2

1Department of Neurology and 2Department of Cell Biology and Physiology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA

p97 and close encounters of every kind: a brief review

I. Dreveny1, V.E. Pye1, F. Beuron, L.C. Briggs, R.L. Isaacson, S.J. Matthews, C. McKeown, X. Yuan, X. Zhang and P.S. Freemont2

Department of Biological Sciences, Centre for Structural Biology, Imperial College London, South Kensington, London SW7 2AZ, U.K.

Valosin-containing protein and the pathogenesis of frontotemporal dementia associated with inclusion body myopathy

Jake B. Guinto · Gillian P. Ritson · J. Paul Taylor ·Mark S. Forman

Transgenic expression of inclusion body myopathy associated mutant p97/VCP causes weakness and ubiquitinated protein inclusions in mice

Conrad C. Weihl1,2,*, Sara E. Miller1, Phyllis I. Hanson2 and Alan Pestronk1

1Department of Neurology and 2Department of Cell Biology and Physiology, Washington University School of Medicine, 660 S. Euclid Avenue, Saint Louis, MO 63110, USA

APOE is a potential modifier gene in an autosomal dominant form of frontotemporal dementia (IBMPFD)

Sarju G. Mehta, MD1,5, Giles DJ. Watts1,5, Jennifer L. Adamson2, Mike Hutton2, Geanie Umberger, PhD3,Shuling Xiong,MD4, Sheena Ramdeen, BSc1, Mark A. Lovell, PhD4, Virginia E. Kimonis,MD1, and Charles D. Smith,MD3

From the 1Children’s Hospital Clinical Genetics and Metabolism, Boston, Massachusetts; 2Mayo Clinic Jacksonville, Jacksonville, Florida; 3Department of Neurology and Sanders-Brown Center on Aging, University of Kentucky, Lexington, Kentucky; 4Department of Chemistry and Sanders-Brown Center on Aging, University of Kentucky, Lexington, Kentucky; 5 These authors contributed equally.

Virginia E. Kimonis, MD, MRCP, Division of Genetics and Metabolism, Department of
Pediatrics, University of California Irvine Medical Center, 101 The City Drive South,
ZC4482, Orange, CA 92686. E-mail: vkimonis@uci.edu
Submitted for publication May 3, 2006.
Accepted for publication October 31, 2006.
Disclosure: The authors reported no conflict of interests.
DOI: 10.1097/GIM.0b013e31802d830d
January 2007 Vol. 9 No. 1 a r t i c l e
Genetics IN Medicine 9

Clinical Studies in Familial VCP Myopathy, Paget Disease of Bone, and Frontotemporal Dementia

Virginia. E. Kimonis1, Sarju G. Mehta1, Erin C. Fulchiero1, Dana Thomasova1, Marzia Pasquali2, Kym Boycott3, Edward G. Neilan1, Alex Kartashov4, Mark S. Forman5, A. Keith W. Brownell3, Stuart Tucker6, Katerina Kimonis1, Steven Mumm7, Michael Whyte7, Charles D. Smith8 and Giles D. J. Watts1

1 Division of Genetics and Metabolism, Children's Hospital, Harvard Medical School, Boston, MA.
2 Department of Pathology, School of Medicine, University of Utah, Salt Lake City, UT.
3 University of Calgary, Alberta Children’s Hospital, Calgary, AB, Canada.
4 Clinical Research Program (CRP), Division of Biostatistics, Children’s Hospital, Boston, MA.
5 Division of Neuropathology, Department of Pathology and Laboratory Medicine, University of Pennsylvania, PA
6 Eastover Internal Medicine, Carolinas HealthCare System, Charlotte, NC.
7 Division of Bone and Mineral Diseases, Washington University School of Medicine and Barnes-Jewish Hospital Research Institute, St. Louis, MO.
8 Department of Neurology and Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY.
 
Corresponding Author:           Virginia E. Kimonis, MD, MRCP
University of California, Irvine
Division of Genetics and Metabolism
Department of Pediatrics
101 The City Drive, ZOT 4482
Orange, CA 92868
Tel: (714) 456-2942
Fax :(714) 456 5610
Email:vkimonis@uci.edu

 

VCP Associated Inclusion Body Myopathy and Paget Disease of Bone Knock-In Mouse Model Exhibits Tissue Pathology Typical of Human Disease

Mallikarjun Badadani1., Ange` le Nalbandian1., Giles D. Watts2,10., Jouni Vesa1., Masashi Kitazawa3, Hailing Su1, Jasmin Tanaja1, Eric Dec1, Douglas C. Wallace1,4,5,6, Jogeshwar Mukherjee7, Vincent Caiozzo8, Matthew Warman9, Virginia E. Kimonis1* 1 Department of Pediatrics, University of California Irvine, Irvine, California, United States of America, 2 Department of Orthopedic Surgery, Children’s Hospital Boston, Harvard Medical School, Boston, Massachusetts, United States of America, 3 Department of Neurobiology and Behavior, University of California Irvine, Irvine, California, United States of America, 4 Center for Molecular and Mitochondrial Medicine and Genetics, University of California Irvine, Irvine, California, United States of America, 5 Departments of Ecology and Evolutionary Biology, University of California Irvine, Irvine, California, United States of America, 6 Department of Biological Chemistry, University of California Irvine, Irvine, California, United States of America, 7 Department of Psychiatry & Human Behavior, University of California Irvine, Irvine, California, United States of America, 8 Departments of Physiology and Biophysics, and Orthopedics, University of California Irvine, Irvine, California, United States of America, 9 Department of Genetics, Children’s Hospital Boston, Harvard Medical School, Boston, Massachusetts, United States of America, 10 Department of Cell Biology and Biochemistry, School of Medicine, Health Policy and Practice, University of East Anglia, Norwich, Norfolk, United Kingdom

Inclusion Body Myopathy with Paget Disease of Bone and/or Frontotemporal Dementia

Virginia Kimonis, MD, Giles Watts, PhD

The Multiple Faces of Valosin-Containing Protein-Associated Diseases: Inclusion Body Myopathy with Paget's Disease of Bone, Frontotemporal Dementia, and Amyotrophic Lateral Sclerosis

Angele Nalbandian • Sandra Donkervoort • Eric Dec • Mallikarjun Badadani • Veeral Katheria • Prachi Rana • Christopher Nguyen • Jogeshwar Mukherjee • Vincent Caiozzo • Barbara Martin • Giles D. Watts • Jouni Vesa • Charles Smith • Virginia E. Kimonis

Global gene profiling of VCP-associated inclusion body myopathy

Angèle Nalbandian1,* , Svetlana Ghimbovschi2,* , Shlomit Radom-Aizik3 , Eric Dec1 , Jouni Vesa1 , Barbara Martin4 , Susan Knoblach2 , Charles Smith4 , Eric Hoffman2 , and Virginia E.

Kimonis1,#

1 Department of Pediatrics, Division of Genetics and Metabolism, University of California, Irvine, CA, US

2 Children’s National Medical Center, Research Center Genetics Medicine, Washington, DC 20010, USA

3 Department of Pediatrics, Institute for Clinical and Translational Science, University of California, Irvine, CA, USA

4 Department of Neurology, University of Kentucky, Lexington, KY 40536, USA

Genotype-Phenotype studies of VCP-associated Inclusion Body Myopathy with Paget Disease of Bone and/or Frontotemporal Dementia

Sarju G. Mehta1*# , Manaswitha Khare1* , Rupal Ramani1* , Giles D. J. Watts2 , Mariella Simon3 , Kathryn E. Osann4 , Sandra Donkervoort1, 8 , Eric Dec1 , Angele Nalbandian1 , Julia Platt3, 9 , Marzia Pasquali5 , Annabel Wang6 , Tahseen Mozaffar6 , Charles D. Smith7 , and Virginia E. Kimonis1

* These individuals contributed equally to this study.

#East Anglian Regional Genetics Service, Addenbrookes Hospital, Cambridge, UK.

1 Division of Genetics and Metabolism, Department of Pediatrics, University of California, Irvine, CA.

2 Biomedical Research Center, University of East Anglia, Norwich, Norfolk.

3 Mitomed Laboratory, University of California, Irvine, CA.

4 Division of Hematology/Oncology, Department of Medicine, University of California, Irvine, CA.

5 Department of Pathology, School of Medicine, University of Utah, Salt Lake City, UT.

6 ALS and Neuromuscular Center, University of California, Irvine, CA.

7 Department of Neurology and Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY.

8 Sandra Donkervoort is currently at Neuromuscular and Neurogenetic Disorders of Childhood Section, Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of

Health, Bethesda, MD.

9 Julia Platt is currently at Biochemical Genetics, Lucile Packard Children's Hospital, Stanford, CA.

The Homozygote VCPR155H/R155H Mouse Model Exhibits Accelerated Human VCP-Associated Disease Pathology

Angèle Nalbandian1* , Katrina J. Llewellyn1* , Masashi Kitazawa2 , Hong Z. Yin3 , Mallikarjun Badadani1 , Negar Khanlou4 , Robert Edwards5 , Christopher Nguyen1 , Jogeshwar Mukherjee6 , Tahseen Mozaffar3,7 , Giles Watts8 , John Weiss3 and Virginia E. Kimonis1#

1 Department of Pediatrics, Division of Genetics and Metabolism, University of California-Irvine, Irvine, CA 92697, USA

2 School of Natural Sciences, University of California-Merced, Merced, CA 95343, USA

3 Department of Neurology; Anatomy and Neurobiology, University of California-Irvine, Irvine, CA, 92697, USA

4 Department of Pathology and Lab Medicine, University of California-Los Angeles, Los Angeles, CA, 90095, USA

5 Department of Pathology, University of California-Irvine, Irvine, CA, 92697, USA

6 Preclinical Imaging Center, Department of Radiological Sciences, University of California-Irvine, Irvine, CA 92697, USA

7 Department of Orthopedics, University of California-Irvine, Irvine, CA, 92697, USA

8 Cell Biology and Biochemistry, School of Medicine, Health Policy and Practice, Biomedical Research Centre, University of East Anglia, Norwich, Norfolk, UK

VCP Associated Inclusion Body Myopathy and Paget Disease of Bone Knock-In Mouse Model Exhibits Tissue Pathology Typical of Human Disease

Mallikarjun Badadani1. , Angèle Nalbandian1. , Giles D. Watts2,10. , Jouni Vesa1. , Masashi Kitazawa3 , Hailing Su1 , Jasmin Tanaja1 , Eric Dec1 , Douglas C. Wallace1,4,5,6 , Jogeshwar Mukherjee7 , Vincent Caiozzo8 , Matthew Warman9 , Virginia E. Kimonis1 *

1 Department of Pediatrics, University of California Irvine, Irvine, California, United States of America,

2 Department of Orthopedic Surgery, Children’s Hospital Boston, Harvard Medical School, Boston, Massachusetts, United States of America,

3 Department of Neurobiology and Behavior, University of California Irvine, Irvine, California, United States of America,

4 Center for Molecular and Mitochondrial Medicine and Genetics, University of California Irvine, Irvine, California, United States of America,

5 Departments of Ecology and Evolutionary Biology, University of California Irvine, Irvine, California, United States of America,

6 Department of Biological Chemistry, University of California Irvine, Irvine, California, United States of America,

7 Department of Psychiatry & Human Behavior, University of California Irvine, Irvine, California, United States of America,

8 Departments of Physiology and Biophysics, and Orthopedics, University of California Irvine, Irvine, California, United States of America,

9 Department of Genetics, Children’s Hospital Boston, Harvard Medical School, Boston, Massachusetts, United States of America, 10 Department of Cell Biology and Biochemistry, School of Medicine, Health Policy and Practice, University of East Anglia, Norwich, Norfolk, United Kingdom

A Progressive Translational Mouse Model of Human VCP Disease: The VCP R155H/+ Mouse

Angèle Nalbandian, PhD1,* , Katrina J. Llewellyn, PhD1,* , Mallikarjun Badadani, PhD1 , Hong Z. Yin, MD2 , Christopher Nguyen, BS1 , Veeral Katheria, BS1 , Giles Watts, PhD4 , Jogeshwar Mukherjee, PhD3 , Jouni Vesa, PhD1 , Vincent Caiozzo, PhD5 , Tahseen Mozaffar, MD2,5 , John H. Weiss, MD2 , and Virginia E. Kimonis, MD, MRCP1,#

1 Department of Pediatrics, Division of Genetics and Metabolism, 2501 Hewitt Hall, University of California-Irvine, Irvine, CA 92697, USA

2 Department of Neurology, Gillespie Hall, University of California-Irvine, Irvine, CA 92697, USA

3 Preclinical Imaging Center, Department of Radiological Sciences, Medical Science C, University of California-Irvine, Irvine, CA 92697, USA

4 Cell Biology and Biochemistry, School of Medicine, Health Policy and Practice, Biomedical Research Centre, University of East Anglia, Norwich, Norfolk, UK

5 Department of Orthopedics, University of California-Irvine, Irvine, CA, 92697, USA

Lipid-enriched diet rescues lethality and slows down progression in a murine model of VCP-associated disease

Katrina J. Llewellyn1,{, Ange` le Nalbandian1,{,, Kwang-Mook Jung2, Christopher Nguyen1, Agnesa Avanesian2, Tahseen Mozaffar3, Daniele Piomelli2,4 and Virginia E. Kimonis1,

1 Department of Pediatrics, Division of Genetics and Metabolism,

2 Department of Anatomy and Neurobiology and

3 Department of Neurology, Orthopedic Surgery, University of California-Irvine, Irvine, CA 92697, USA and

 4 Drug Discovery and Development, Istituto Italiano di Tecnologia, Genoa 16133, Italy

Valosin containing protein associated inclusion body myopathy: abnormal vacuolization, autophagy and cell fusion in myoblasts 

Jouni Vesa,a Hailing Su,a Giles D. Watts,b Sabine Krause,c Maggie C. Walter,c Douglas C. Wallace,d,e,f and Virginia E. Kimonisa,*

Valosin-containing protein (VCP/p97) inhibitors relieve Mitofusin-dependent mitochondrial defects due to VCP disease mutants

 TingZhang1, PrashantMishra2, BruceAHay2, DavidChan2, MingGuo1,3

 1 Department of Neurology, UCLA David Geffen School of Medicine, University of California, Los Angeles, United States;

 2 Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States;

 3 Department of Molecular and Medical Pharmacology, UCLA David Geffen School of Medicine, University of California, Los Angeles, United States

 

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Contact Monica Smersh with questions.

IBMPFD and ALS:

The following links are to papers that have identified some commonality between some forms of ALS and the same mutations on the VCP gene that are associated with IBMPFD.

Exome Sequencing Reveals VCP Mutations as a Cause of Familial ALS

Janel O. Johnson,1,22 Jessica Mandrioli,4,22 Michael Benatar,5,22 Yevgeniya Abramzon,1,22 Vivianna M. Van Deerlin,6 John Q. Trojanowski,6 J. Raphael Gibbs,2,8 Maura Brunetti,9 Susan Gronka,5 Joanne Wuu,5 Jinhui Ding,2 Leo McCluskey,7 Maria Martinez-Lage,6 Dana Falcone,6 Dena G. Hernandez,8,3 Sampath Arepalli,3 Sean Chong,3 Jennifer C. Schymick,1 Jeffrey Rothstein,10 Francesco Landi,11 Yong-Dong Wang,12 Andrea Calvo,13 Gabriele Mora,14 Mario Sabatelli,15 Maria Rosaria Monsurro,16 Stefania Battistini,17 Fabrizio Salvi,18 Rossella Spataro,19 Patrizia Sola,4 Giuseppe Borghero,20 The ITALSGEN Consortium,23 Giuliana Galassi,4 Sonja W. Scholz,3,21 J. Paul Taylor,12 Gabriella Restagno,9,24 Adriano Chio,13,24 and Bryan J. Traynor1,10,24,

* 1Neuromuscular Diseases Research Group 2Computational Biology Core  3Molecular Genetics Unit Laboratory of Neurogenetics, Porter Neuroscience Building, NIA, NIH, Bethesda, MD 20892, USA  4Department of Neuroscience, S. Agostino-Estense Hospital and University of Modena, 41126 Modena, Italy  5Department of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA  6Department of Pathology and Laboratory Medicine  7Department of Neurology University of Pennsylvania, Philadelphia, PA 19104, USA  8Department of Molecular Neuroscience and Reta Lila Weston Laboratories, Institute of Neurology, University College London, London WC1 3BG, UK  9Molecular Genetics Unit, Department of Clinical Pathology, A.S.O. O.I.R.M.-S. Anna, 10126 Turin, Italy  10Department of Neurology, Johns Hopkins Hospital, Baltimore, MD 21287, USA  11Department of Gerontology, Geriatrics, and Rehabilitative Medicine, Catholic University of Sacred Heart, Rome, Italy  12Department of Developmental Neurobiology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA  13Department of Neuroscience, University of Turin, 10126 Turin, Italy  14ALS Center, Salvatore Maugeri Foundation, 20100 Milan, Italy  15Neurological Institute, Catholic University and I.C.O.M.M. Association for ALS Research, 10100 Rome, Italy  16Department of Neurological Sciences, Second University of Naples, 80138 Naples, Italy  17Department of Neuroscience, Neurology Section, University of Siena, 53100 Siena, Italy  18Center for Diagnosis and Cure of Rare Diseases, Department of Neurology, Bellaria Hospital, 40100 Bologna, Italy  19Department of Clinical Neurosciences, University of Palermo, 90129 Palermo, Italy  20Neurological Clinic, Azienda Hospital, University of Cagliari, 09042 Monserrato-Cagliari, Italy  21Department of Neuroscience, Georgetown University, Washington, D.C. 20057, USA  22These authors contributed equally to this work  23For a list of consortium members, please see the Supplemental Information  24These authors contributed equally to this work

Capturing VCP: Another Molecular Piece in the ALS Jigsaw Puzzle

Christopher E. Shaw1,* 1King’s College London, MRC Centre for Neurodegeneration Research, Department of Clinical Neuroscience, Institute of Psychiatry, London SE5 8AF, UK

*Correspondence: christopher.shaw@kcl.ac.uk

Books

Stratmann, H.G., Using Medicine in Science Fiction The SF Writer's Guide to Human Biology, Springer, 2016. Given that a treatment for IBMPFD is probably 10-25 years in the future and a cure for IBMPFD is 25-100 years in the future, any discussion of a treatment or cure for IBMPFD is now in the realm of science fiction. This book provides very good descriptions of what is currently thought to be possible along with reasonable explanations of the technical difficulties to be overcome. The funding problems and government impediments are obliquely noted. The books does mention "ethical" issues, but only in the very narrow and limited medical practicioner perspective, i.e., not from a general philosophical perspective (most would consider the position to be that of the morals of the medical organization).

General Information:

This paper is about edema.

The following papers are for general information about amino acids:

DNA codons for Amino Acids Table

Amino Acid Symbols

Amino Acid Properties

Biochemistry of Amino Acids

Lectures on Genetics

Newspaper listings:

This link is to a newspaper article about fruit-fly research, published 28 June 2010: Tom Avril Article The following is an excerpt:

Muscle, bone, and brain

You've never heard of the disease that Ritson and Taylor are studying, and your doctor almost certainly hasn't, either.

It's a mouthful: inclusion body myopathy associated with Paget's disease of bone and frontotemporal dementia. IBMPFD for short.

It is caused by mutations in one gene, yet patients can have symptoms of up to three separate diseases reflected in the name: withered muscles, aching bones and dementia.

Just a few hundred people have been found to have the disease, though likely many more remain to be identified, said Virginia Kimonis, professor at the University of California Irvine. She was part of a team that discovered the disease in 2000. In 2004, she found the gene that, when mutated, would cause it.

But finding the genetic culprit for a disease is just a first step in a tedious process. Physicians can't "turn off" or replace individual genes in people, for the most part, nor would they want to without figuring out exactly what the gene does. Genes tend to have multiple functions and do not operate in isolation.

Instead, researchers seek to identify the "cascade" leading to a disease: a series of molecular events involving the interaction of many genes. By looking at various points "upstream" and "downstream" of a flawed gene, they hope to find a spot where it would be easy to dam up the river - without unwanted side effects.

 

The following papers are specific to me:

Biopsy Report  This is the results of a needle biopsy (relatively painless) performed on David Sweetman at the University of Rochester in 2002 in one of the attempts to determine the nature of the disease (before the discovery of the VCP mutations noted above).

Failure Analysis of IBMPFD  This is a "non-medical" paper written by David Sweetman in an attempt to put medical concepts into a format better understood by one whose background is in manufacturing or assembly.  All comments are welcome, both to correct any errors as well as suggestions for improvement or addition of other information.