Jeremie Martinet, PharmD, PhD
Immunoglobulins for neuromuscular disorders: immunomodulation and myoregeneration by IVIg in immune-mediated necrotising myopathy (myoRIg)
Immune-mediated necrotising myopathies (IMNMs) are a severe form of autoimmune myopathy associated with the presence of pathogenic autoantibodies (aAbs). Clinically, IMNMs are characterized by severe, symmetrical, proximal muscle weakness. Other symptoms may include dysphagia, dyspnea, interstitial lung disease and Raynaud's syndrome. Current treatments are largely empirical and suboptimal and frequently utilize corticosteroids with or without immunosuppressants and intravenous immunoglobulins (IVIg). The mechanism of action for IVIg in treating IMNMs is unknown. IMNMs are associated with aAbs directed against signal recognition particle (SRP) or HMG-CoA reductase (HMGCR) proteins. In our laboratory, we demonstrated that anti-SRP aAbs are pathogenic and crucial to disease development. Preliminary results suggest that IVIg may have a pro-myogenic effect (stimulating muscle regeneration) while anti-SRP aAbs may have the opposite effect.
The aim of this study is to investigate the mechanism of the therapeutic effects of IVIg in IMNMs. We will first confirm the positive effects of IVIg on muscular regeneration. Then, we will evaluate the therapeutic effect of IVIg in a model of IMNMs developed in our laboratory. This study will improve our understanding of the mechanism of action of IVIg in IMNM treatment. This study should also lead to improved IMNM treatment through a better understanding of the therapeutic effects of IVIg and optimization of the use of this therapy.
Jérémie Martinet completed his pharmaceutical degree in 2011 at the University of Grenoble (France). He completed his residency in Immunology and Biotherapy at the Grenoble University Hospital. During his residency, he worked in the field of immunotherapy. He completed his PhD thesis at the Blood Bank Centre in Grenoble on the therapeutic effects of plasmacytoid dendritic cells in hepatitis B virus (HBV) infection. He successfully defended his thesis in 2012.
In 2011, he joined the team of Professor Olivier Boyer (INSERM unit 1234) at the Rouen University Hospital as an Assistant Professor to study neuromuscular autoimmunity (myositis) and the diagnosis of myositis. His studies focused on the pathologic role of autoantibodies in immune-mediated necrotising myositis and particularly on anti-SRP and anti-HMGCR aAbs.
Currently, he is developing new immunotherapies for autoimmune diseases and contributing to myositis diagnostics as an Associate Professor in the Immunology and Biotherapy Laboratory at Rouen University Hospital.