Myositis are autoimmune diseases that affects the muscles and are often associated with extra-muscular involvement (e.g., skin, joints, or lungs). Thus, myositis is a group of disorders that either involve only the muscles or are systemic diseases. These conditions can be spontaneous or triggered by cancer and/or treatments (e.g., cholesterol-lowering drugs or cancer immunotherapies). They are serious diseases that can lead to disability or even be life-threatening. Treatment combines usually corticosteroids and immunosuppressants, but without targeted approaches and without considering the specificities of myositis subgroups.

Our objective is to improve the diagnostic and therapeutic management of myositis.

Our approach is translational: from the laboratory to the patient and from the patient back to the laboratory.

Our team consists of expert physicians/researchers in myositis, research engineers, biostaticians, doctoral candidates, and postdoctoral fellows.

We have established a biobank containing biological samples from over 1,500 myositis patients, alongside associated medical data. In our laboratory, we have an outstanding research environment focused on muscle and autoimmune diseases, allowing for the analysis of samples and in vitro experimentation, particularly using muscle cell culture models, to achieve our aims.

Our research focuses on three main areas:

(i) Defining homogeneous patient groups, (ii) analyzing at the tissue-level pathophysiological mechanisms, and (iii) developing innovative diagnostic and therapeutic tools.

 1- Nosological framework : Identify your opponents

As a prerequisite for any research work, it is necessary to define homogeneous patient groups with common pathomechanisms.

Over the last 10 years, we have been at the forefront of revising the international diagnostic criteria for the main subgroups of myositis (dermatomyositis, immune-mediated necrotizing myopathy, and anti-synthetase syndrome). We have demonstrated, with others, the crucial role of myositis specific antibodies to diagnose and classify myositis patients into homogeneous groups and organized conference consensus on the detection methods for myositis specific autoantibodies (ENMC 2021 criteria). We also contributed to the workshop refining the diagnosis criteria for inclusion body myositis (ENMC 2023 criteria).

We were also pioneers in describing a new subgroup of myositis induced by immune checkpoint inhibitors (ICIs), whose use represents a major advancement in cancer treatment. We have reported the largest series of ICI-induced myositis, demonstrating that the disease differs from spontaneous myositis in terms of phenotype and high mortality rate.  Indeed, in recent years, a new form of myositis has emerged combining severe muscle and heart manifestations. Naturally, our team has expanded with the addition of a world-renowned cardiologist expert (Pr Salem) in the cardiac toxicity of anti-cancer drugs and myocarditis induced by anti-tumor immunotherapy.

2- Clarify the pathomechanism: Identify the weaknesses of your opponent

We have contributed to demonstrating the pathogenic role of autoantibodies in myositis, particularly in the most disabling form, immune-mediated necrotizing myopathy. We were also pioneers in demonstrating the pathogenic role of type I interferon in dermatomyositis.

These studies led us to closely analyze the characteristics of muscle inflammation in tissue, and, more importantly, its effect on muscle fibers.

To improve our understanding, we had to develop and learn to use RNA sequencing tools at the single-nucleus or single-cell level, using enzymatically digested tissue, but also preserving tissue architecture (spatial transcriptomics) in order to analyze cellular interactions. These extensive molecular data need to be validated at the protein level. Therefore, we have established multiplex imaging analyses using Imaging Mass Cytometry (Hyperion®) or are conducting international collaborations for mass spectrometry analyses.

These studies allowed us to understand the pathophysiological mechanisms of myositis induced by immunotherapy, highlighting the important role of resident immune cells in the muscle.

These techniques also enabled us to demonstrate the significance of non-inflammatory resident cells in muscle tissue in the pathological mechanisms and their impact on muscle cell regeneration. These results lead us to analyze the effect of inflammation on the muscle microenvironment by testing hypotheses using 3D culture models.

3- Develop a new therapeutic strategy: Defeat one’s enemy

From the laboratory, we return to the patients to propose therapeutic solutions.

Over the past 10 years, our research has led to innovative controlled clinical trials (academic or industrial) for each subgroup of myositis: inclusion body myositis, necrotizing autoimmune myopathies, anti-synthetase syndrome, and dermatomyositis. As exemple, in dermatomyositis anti-interferon approaches using JAK inhibitors are tested in a randomized control trial (PHRC 2018; PI Y. Allenbach).

The studies we conducted also led to developments abroad, such as the international phase III trial testing rapamycin in inclusion body myositis (NCT04789070).

Among the latest advancements we are working on, we are proposing an innovative therapy to treat the muscular and cardiac complications of immunotherapy, as well as studies in regenerative medicine through cell therapy for inclusion body myositis.

We recently proposed to restore muscle strength using cell therapy with the stromal vascular fraction (rich in stem cells). This cell extract obtained from adipose tissue can differentiate into several lineages, including muscle tissue. We were awarded a grant (PHRC-N 2018; NCT05032131 PI O. Benveniste) to conduct a Phase I clinical trial to test the effect of injecting patients with non-dominant inclusion arm myositis with their autologous stromal vascular fraction cells obtained from adipose tissue (after liposuction).

We have shown that CTLA4-Ig (Abatacept) can help patients with severe concomitant myositis and myocarditis (Salem 2023). A therapeutic trial is currently ongoing (NCT05195645, PI JE Salem) to test Abatacept in an RCT for patients with severe irAE.