Gene therapy for myositis
The inflammatory myopathies, polymyositis (PM), dermatomyositis (DM) and inclusion body myositis (IBM), lead to moderate to severe muscle weakness and are characterised by the presence of endomysial inflammation. Each entity has unique clinical, immunopathological and histological characteristics which are associated with different responses to therapies and prognosis. In DM and PM, first-line treatment options include oral corticosteroids, other immunosuppressant drugs, and intravenous immunoglobulins. Patients with IBM, by contrast, usually show a poor or no response to immunomodulatory treatments. Patients with IBM and non-responding patients with PM and DM are candidates for alternative treatment options and experimental therapies including gene therapy. The genetic treatment of inflammatory muscle disorders could involve at least two different strategies: first, to ectopically express local immune modulatory, notably immunosuppressive molecules which would limit inflammation and autoimmunity more effectively than systemic immunosuppressive treatment; second, strategies to promote the repair or allow for the replacement of damaged muscle might be envisaged. Immunosuppressive molecules might include HLA-G, a non-classical major histocompatibility (MHC) Class I molecule, or other cell surface molecules which negatively modulate immune effector cell function. Muscle regeneration might be promoted by myotrophic factors including utrophin or insulin-like growth factors. In addition, cell-based therapies using stem cells or myoblasts might have a therapeutic potential in neuromuscular disorders.
KeywordsDuchenne Muscular Dystrophy Duchenne Muscular Dystrophy Inclusion Body Myositis Inflammatory Myopathy Idiopathic Inflammatory Myopathy
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