Ingrid E Lundberg
Chronic rheumatic muscle inflammation, myositis
Description of the project
Polymyositis and dermatomyositis are chronic, rheumatic diseases characterized by muscle weakness, low muscle endurance and by inflammation in muscle tissue. Conventional immunosuppressive therapy has limited effects and most patients are left with chronic muscle weakness with significant impact on quality of life. Through our translational research project we have demonstrated that both immune and non-immune mechanisms may contribute to muscle weakness in these patients.
The overall aim of this study is to pursue earlier observations of a likely role of proinflammatory cytokines, eg interleukin (IL)-1 and also continue to investigate the influence of non-immune mechanisms, endoplasmic reticulum (ER) stress and hypoxia which could lead to an acquired metabolic myopathy.
Work plan and methods
The effects of targeted therapies (pharmacological treatment (IL-1 blockade) and exercise) will be assessed by the same validated clinical outcome measures in combination with gene expression profiling by microarray analyses, proteomics, and immunohistochemistry in repeated muscle biopsies. In addition, to test the hypoxia hypothesis we will measure muscle metabolites in vivo by microdialysis technique before and after exercise and compare the results in patients with healthy controls. Increased knowledge of key molecular pathways is essential to improve treatment for these patients.
This will be achieved through:
- Clinical longitudinal studies
- Studies in animal models
- In vitro experiments
- The Swedish Research Council
- ALF project Stockholm county
- King Gustaf V 80-year foundation
- The Swedish Rheumatism Association
- The Myositis Association
- Autocure, EU grant, 6th Framework
- NIH, National institute of health
- Roche AB, Sweden
- American College of Rheumatology
- EULAR, The European league against rheumatism
- AFM Association Francaise contre les Myopathies
- The Swedish Research Council network funds, SVEMYONET
The research group
- Ingrid Lundberg, group supervisor
- Eva Lindroos, biomedical scientist
- Christina Ottosson, nurse
- Björn Löfström, PhD student
- Christina Dorph, PhD student
- Ingela Loell, PhD student
- Jayesh Pandya, graduate student
- Li Alemo Munters, PhD student
- Malin Regardt, PhD student
- Andreas Fasth, post doc
- Helene Alexandersson, post doc
- Maryam Dastmalchi, post doc
- Maryam Fathi, post doc
- Sevim Barbasso Helmers, post doc
Five selected publications
A high incidence of flares in an open pilot study of infliximab in patients with inflammatory myopathies.
Ann Rheum Dis. 2008 Feb 13. [Epub ahead of print].
Immunolocalization of interleukin-1 receptors in the sarcolemma and nuclei of skeletal muscle in patients with idiopathic inflammatory myopathies.
Arthritis Rheum. 56:674-87, 2007.
Benefits of intensive resistance training in patients with chronic polymyositi or dermatomyositis.
Arthritis Rheum. 57:768-77, 2007.
A possible mechanism for endogenous activation of the type I interferon system in myositis patients with anti-Jo-1 or anti-Ro52 autoantibodies.
Arthritis Rheum, 56:3112-3124, 2007.
Technology Insight: Tools for research, diagnosis and clinical assessment of treatment in idiopathic inflammatory myopathies.
Nature Clin Pract Rheumatol, 3:282-90, 2007 (Review).