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Myositis Research

Our Myositis Research has had a longstanding focus of the investigation of clinical, genetic and immunological aspects of the inflammatory myopathies (IBM), with a particular focus on inclusion body myositis, the most common muscle disease associated with aging. The inflammatory myopathies are a rare group of diseases that involve chronic muscle inflammation (myositis), accompanied by muscle weakness. Chronic inflammatory myopathies are autoimmune disorders, in which the body’s white blood cells (that normally fight disease) attack normal muscle fibres, and other tissues.

Research Focus

The research team is investigating the different causes of myositis, particularly focusing on genetic pre-disposing factors, by looking at myositis patient DNA, and finding common genes. The research team was responsible for the first population-based controlled study of serum autoantibody profiles in IBM, which showed that some HLA-DRB alleles are protective, while other alleles are associated with increased risk. Similarly, the research team established that the very long poly-T repeat length in the rs10524523 polymorphism of the mitochondrial TOMM-40 gene is associated with a reduced risk of developing IBM and a later age of symptom onset. Studies on transgenic mice have shown that, although there is increased expression of the β-amyloid precursor protein in muscle, this does not lead to deposition of amyloid or other histological changes typical of IBM.

The research team focuses on finding the best diagnostic techniques to facilitate early diagnosis of IBM as well as exploring the complications of myositis, including respiratory complications.

Members

Achievements

PUBLICATIONS

  • Clinical Utility Gene Card for: Becker muscular dystrophy. Coote D, Davis MR, Cabrera M, Needham M, Laing NG, Nowak KJ. Eur J Hum Genet. 2018; 26(7):1065-1071. doi: 10.1038/s41431-017-0064-4.
  • Advances in inclusion body myositis: genetics, pathogenesis and clinical aspects. Needham M, Mastaglia F Expert Opinion on Orphan Drugs, Volume 5, Issue 5, 4 May 2017, Pages 431-443 [Scimago – Quartile, Q2; Rank, 14,070]
  • A Systematic Review and Meta-Analysis of Prevalence Studies of Sporadic Inclusion Body Myositis. Callan, A., Capkun, G., Vasanthaprasad, V., Freitas, R., Needham, M Journal of Neuromuscular Diseases 4(2), pp. 127-137, 2017 [Scimago – Quartile, Q2; Rank, 6,261]
  • Recognition of giant cell arteritis in patients with polymyalgia rheumatica who have a stroke: a cautionary tale, Gutteridge DH, Mastaglia FL, Internal Medicine Journal (accepted for publication November 2016).
  • Sporadic Inclusion Body Myositis: A Review of Recent Clinical Advances and Current Approaches to Diagnosis and Treatment, Needham M, Mastaglia F, Clinical Neurophysiology. 2016; 127(3)1764-1773. PMID:26778717
  • Immunotherapies for Immune-Mediated Myopathies. A Current Perspective. Needham M, Mastaglia FL, Neurotherapeutics. 2016; 13(1):132-146. PMID:26586486. PMCID:4720681.
  • Proposal for a Candidate Core Set of Fitness and Strength Tests for Patients with Childhood or Adult Idiopathic Inflammatory Myopathies. van der Stap DK, Rider LG, Alexanderson H, Huber AM, Gualano B, Gordon P, van der Net J, Mathiesen P, Johnson LG, Ernste FC, Feldman BM, Houghton KM, Singh-Grewal D, Kutzbach AG, Munters LA, Takken T; International Myositis Assessment and Clinical Studies Group (including Mastaglia F). Journal of Rheumatology 2016; 43(1):169-176. PMID:26568594. PMCID:4698199
  • Diagnostic performance of a commercial Immunoblot assay for myositis antibody testing. Bundell C, Rojana-udomsart A, Mastaglia F, Hollingsworth P, McLean-Tooke A. Pathology. 2016; 48(4); 363-366. PMID:27114370
  • Mortality and causes of death in patients with sporadic inclusion body myositis: survey study based on the clinical experience of specialists in Australia, Europe and the USA. Price MA, Barghout V, Benveniste O, Christopher-Stine L, Corbette A, de Visser M, Hilton-Jones D, Kissel JT, Lloyd TE, Lundberg IE, Mastaglia F, Mozaffar T, Needham M, Schmidt J, Sivakumar K, DeMuro C, Tseng BS. Journal of Neuromuscular Disorders. 2016; 3(1):67-75
  • Serum high-density lipoprotein is associated with better cognitive function in a cross-sectional study of aging women. Bates KA, Sohrabi HR, Rainey-Smith SR, Weinborn M, Bucks RS, Rodrigues M, Beilby, Howard M, Taddei K, Martins G, Paton A, Shah T, Dhaliwalh SS, Foster JK, Martins IJ, Lautenschlager NT, Mastaglia FL, Gandy S, Martins RN. International Journal of Neuroscience. 2016 April 25. [Epub ahead of print]. DOI:10.1080/00207454.2016.1182527
  • Rare variants in SQSTM1 and VCP genes and risk of sporadic inclusion body myositis. Gang Q, Bettencourt C, Machado PM, Brady S, Holton JL, Pittman AM, Hughes D, Healy E, Parton M, Hilton-Jones D, Shieh PB, Needham M, Liang C, Zanoteli E, de Camargo LV, De Paepe B, De Bleecker J, Shaibani A, Ripolone M, Violano R, Moggio M, Barohn RJ, Dimachkie MM, Mora M, Mantegazza R, Zanotti S, Singleton AB, Hanna MG, Houlden H, The Muscle Study Group and The International IBM Genetics Consortium (including Mastaglia F). Neurobiology of Aging. 2016; 47:218.e1-218.e9. doi: 10.1016/j.neurobiolagingBook ChapterChapter 122: Inclusion body myositis. In: Lisak RP, Truong DD, Carroll WM, Bhidayasiri R, editors Needham M, Mastaglia FL. International Neurology, 2nd edition. John Wiley & Sons, Chichester, UK; 2016. p.505-507
  • Mastaglia, F.L. & Needham, M. (2015) Inclusion body myositis: A review of clinical and genetic aspects, diagnostic criteria and therapeutic approaches
 Journal of Clinical Neuroscience 22 (1), pp. 6-13
  • Silbert, B.I., Heaton, A.E., Cash, R.F.H., James, I.R., Dunne, J.W., Lawn, N.D., Silbert, P.L., Mastaglia, F.L. & Thickbroom, G.W. (2015). Evidence for an excitatory GABAA response in human motor cortex in idiopathic generalised epilepsy, Seizure, 26 (1), pp. 36-42.
  • De Bleecker, J.L., De Paepe, B., Aronica, E.M., De Visser, M., Amato, A., Benveniste, O., De Bleecker, J.L., De Boer, O., Dimachkie, M.M., Ghérardi, R.K., Goebel, H.H., Hilton- Jones, D., Holton, J.L., Lundberg, I.E., Mammen, A., Mastaglia, F.L., Nishino, I., Mammen, A.L., Daa Schroder, H., Selcen, D. & Stenzel, W. (2015). 205th ENMC International Workshop: Pathology diagnosis of idiopathic inflammatory myopathies Part II 28-30 March 2014, Naarden, The Netherlands, Neuromuscular Disorders, 25 (3), pp. 268-272.
  • Johnson, L., Rodrigues, J., Teo, W.-P., Walters, S., Stell, R., Thickbroom, G., Mastaglia, F. (2015) Interactive effects of GPI stimulation and levodopa on postural control in Parkinson’s disease Gait and Posture 41 (4), pp. 929-934.
  • Sohrabi, H.R., Bates, K.A., Weinborn, M., Bucks, R.S., Rainey-Smith, S.R., Rodrigues, M.A., Bird, S.M., Brown, B.M., Beilby, J., Howard, M., Criddle, A., Wraith, M., Taddei, K., Martins, G., Paton, A., Shah, T., Dhaliwal, S.S., Mehta, P.D., Foster, J.K., Martins, I.J., Lautenschlager, N.T., Mastaglia, F., Laws, S.M. & Martins, R.N. (2015) Bone mineral density, adiposity, and cognitive functions Frontiers in Aging Neuroscience 7 Issue FEB, Article 16.
  • Huang, Y., Wang, G. , Rowe, D., Wang, Y., Kwok, J.B.J., Xiao, Q., Mastaglia, F., Liu, J., Chen, S.-D. & Halliday, G. (2015) SNCA gene, but not MAPT, influences onset age of Parkinson’s disease in Chinese and Australians BioMed Research International 2015, 135674
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  • Luo, Y.-B. & Mastaglia, F.L. (2015) Dermatomyositis, polymyositis and immune-mediated necrotising myopathies Biochimica et Biophysica Acta – Molecular Basis of Disease 1852, pp. 622-632.
  • Limaye, V., Bundell, C., Hollingsworth, P., Rojana-Udomsart, A., Mastaglia, F., Blumbergs, P. & Lester, S. (2015) Clinical and genetic associations of autoantibodies to 3-hydroxy-3-methyl-glutaryl-coenzyme a reductase in patients with immune-mediated myositis and necrotizing myopathy Muscle and Nerve – Article in press
  • Anderton RS, Meloni BP, Mastaglia FL, Boulos S.  2014. Investigation of a recombinant SMN protein delivery system to treat spinal muscular atrophy. Translational Neuroscience. 2014; 5(1):8-16.
  • Edwards DJ, Dipietro L, Demirtas-Tatlidede A, Medeiros AH, Thickbroom GW, Mastaglia FL, Krebs HI, Pascual-Leone A.  Movement-generated afference paired with transcranial magnetic stimulation: an associative stimulation paradigm.  J Neuroengineering & Rehabilitation  2014; 11:31.
  • Greene ID, Mastaglia F, Meloni BP, West KA, Chieng J, Mitchell CJ, Gai WP, Boulos S.  Evidence that the LRRK2 ROC domain Parkinson’s disease-associated mutants A1442P and R1441C exhibit increased intracellular degradation.  J Neuroscience Research 2014; 92(4):506-516.
  • Greer KL, Lochmuller H, Flanigan K, Fletcher S, Wilton SD. Targeted exon skipping to correct exon duplications in the dystrophin gene. Molecular therapy Nucleic acids 2014; 3:e155.
  • Huang Y, Wang G, Rowe D, Wang Y, Kwok J B J, Xiao Q, Mastaglia FL.  SNCA Gene, but Not MAPT, Influences Onset Age of Parkinson’s Disease in Chinese and Australians.  Biomedical Research International. Vol 2014, Article ID 135674, 6 pages.
  • Kakulas BA, Kaelan C. The neuropathological foundations for the restorative neurology of spinal cord injury.  Clinical Neurology and Neurosurgery, 128 S1  PP 51-57.
  • Kanyenda LJ, Verdile G, Martins RN, Meloni BP, Chieng, J, Mastaglia FL, Laws SM, Anderton RS, Boulos, S. (2014). Is cholesterol and Aβ stress induced CD147 expression a protective response?: evidence that extracellular cyclophilin A mediated neuroprotection is reliant on CD147. Journal of Alzheimer’s Disease 39, 545–556.
  • Limaye V, Bundell C, Hollingsworth P, Rojana-Udomsart A, Mastaglia FL, Blumbergs P, Lester S. The clinical and genetic associations of autoantibodies to HMGCR in patients with immune-mediated myositis and necrotizing myopathy.  Muscle & Nerve.  2014 Dec 18.
  • Luo YB, Mastaglia FL, Wilton SD.  Normal and aberrant splicing of LMNA.  J Medical Genetics 2014; 51(4): 215-223.
  • Luo YB, Mastaglia FL.  Dermatomyositis, polymyositis and immune-mediated necrotising myopathies. Biochim Biophys Acta. 2014 Jun 4. pii: S0925-4439(14)00162-8.
  • Luo YB, Mitrpant C, Adams AM, Johnsen RD, Fletcher S, Mastaglia FL, Wilton SD.  Antisense oligonucleotide induction of progerin in human myogenic cells.  PLoS ONE. 2014; 9(6):e98306.
  • Mastaglia FL, Needham M.  Inclusion body myositis: A review of clinical and genetic aspects, diagnostic criteria and therapeutic approaches.  Journal of Clinical Neuroscience 2014; [Epub ahead of print]  pii: S0967-5868(14)00619-5.
  • Meloni BP and Knuckey NW (2014). Magnesium may provide further benefit to hypothermia following perinatal asphyxia encephalopathy. Journal of Perinatal Medicine, 43, 125-126. Letter to the Editor.
  • Needham M, Mastaglia FL.  Statin myotoxicity: a review of genetic susceptibility factors.  Neuromuscular Disorders.  2014; 24(1):4-15.
  • Rodriguez CPM, Needham M, Hollingsworth P, Mastaglia FL, Hillman DR.  Sleep disordered breathing and subclinical impairment of respiratory function are common in sporadic inclusion body myositis.  Neuromuscular Disorders  2014; 24(12):1036-1041.
  • Rodriguez Cruz PM, Luo YB, Miller J, Junckerstorff RC, Mastaglia FL, Fabian V. An analysis of the sensitivity and specificity of MHC-I and MHC-II immunohistochemical staining in muscle biopsies for the diagnosis of inflammatory myopathies. Neuromuscular Disorders 2014; 24:1025-1035.
  • Strautins K, Tschochner M, James I, Choo L, Dunn DS, Pedrini M, Kermode A, Carroll W, Nolan, D. Combining HLA-DR and anti-Epstein-Barr antibody. Multiple Sclerosis Journal 2014;20(3):286-294.
  • Teo WP, Rodrigues JP, Mastaglia FL, Thickbroom GW.  Modulation of corticomotor excitability after maximal or sustainable-rate repetitive finger movement is impaired in Parkinson’s disease and is reversed by levodopa.  Clinical Neurophysiology 2014; 125(3):562-568.

GRANTS

NHMRC 2010 – 2013

Definition of dystrophin functional domains according to exon boundaries to optimise splice switching therapies for Duchenne muscular dystrophy $520,764

National Institute Health (NIH) 2010 – 2012

Antisense oligonucleotide suppression of non-deletion DMD causing mutations
$808,295

Muscular Dystrophy Association (USA) 2010 – 2012

Preclinical assessments of splice switching oligomers
$342,668

Duchenne Ireland 2010 – 2012

Personalised exon skipping for the treatment of DMD
$144,677

Action Duchenne 2010 – 2012

Exon Skipping of important parts of the dystrophin gene message
$125,431