The year 2020 was marked by new projects and key achievements, especially in the context of the implementation of the Strategic Plan, reflecting the dynamism of the Institute and its teams’ commitment to a common set of goals: the benefit of the patient, recognition for the field of Myology and scientific advances in the successful treatment of neuromuscular disease.
01 / ASSESSMENT OF THE INSTITUTE OF MYOLOGY
The “Scientific Advisory Board” (SAB), an international committee made up of nine independent experts, gave a positive assessment of the Institute of Myology in 2020, and recognised it as “one of the best neuromuscular disease research centres in the world, if not the best”. According to these experts, cross-sectional research at this institution is active and structured, and it was noted that there is very good cooperation between teams, with real and unique expertise. The construction of a new building, which will allow all the experts to be gathered in one place and the number of research teams to be increased, will only strengthen our ambition for scientific and medical excellence, as we move towards the creation of the Myology Foundation.
02 / MYOLOGY RESEARCH CENTRE
Teams from the Centre for Research have continued the work started in the development of innovative therapies for neuromuscular disease: genetic and pathophysiological development, preclinical and clinical therapeutic approaches, and neuromuscular disease biotherapies. The Myoline, Myoimage and Myovector platforms, which arose from the Research Centre teams, have been organised in order to harmonise methods, so as to facilitate later large-scale production in the context of preclinical and subsequent clinical trials.
03 / CENTRE FOR NEUROMUSCULAR INVESTIGATION AND ASSESSMENT
> NMR IMAGING AND SPECTROSCOPY LABORATORY
This laboratory has put in place a protocol for imaging and international multi-centre data processing, for Généthon laboratory projects involving limb-girdle muscular dystrophy due to FKRP deficiency (LGMD R9) and Duchenne muscular dystrophy (DMD).
The laboratory obtained funding from the ANR (French National Research Agency) for its methodological project for the rapid and simultaneous assessment of fat percentage and T1, a parameter that reflects disease activity.
The team has published a dynamic MRI method that can simultaneously measure muscle perfusion and energy metabolism during exercise.
> HISTOPATHOLOGICAL LABORATORY
This laboratory has identified and characterised several forms of congenital myopathy and has contributed to the discovery of myopathies linked to 2 new genes, UNC-45B and GGPS1.
A first database with unprecedented images of the muscle, “The Muscle Atlas“, was created in collaboration with the Centre for Research. It lists, exhaustively and in a qualified manner, more than 4300 muscle biopsies of patients or animals with neuromuscular disease, both treated and untreated. The goal of this collaborative tool is to speed up research, diagnosis and the pursuit of therapeutic avenues.
> NEUROMUSCULAR PHYSIOLOGY AND EVALUATION LABORATORY
This laboratory has validated and published several innovative methods: ElecMyo, to measure muscle volume using an original bioimpedancemetry technique, several non-invasive methods to assess diaphragm dysfunction using ultrasound imaging tools, the validation of MyoGrip in the longitude follow up of patients with Duchenne muscular dystrophy, and also MyoQuad, a device to measure quadriceps strength.
In 2020, Myobank-AFM participated in a gene therapy trial in DMD supported by Généthon, and processed samples from the first patient in the Aspiro gene therapy trial in myotubular myopathy.
The French Ministry of Higher Education, Research and Innovation granted MYOBANK-AFM permission to export and import muscle samples for the teams involved in the international project for the standardised comparison of cell candidates for cell therapy, supported by AFM-Téléthon.
04 / CLINICAL TRIALS
> In 2020, I-Motion Children, the paediatric clinical trial platform, managed 111 patients, enrolled in 19 clinical research protocols, including 2 gene therapy trials and 4 natural history studies, involving 10 different sponsors. These protocols involved Duchenne muscular dystrophy (DMD), spinal muscular atrophy (SMA) and myotubular and centronuclear myopathy.
> The new I-Motion Adults clinical trial platform, created at the end of 2019 to allow clinical trials in adult neuromuscular disease patients to be managed, has gone from strength to strength.
Three studies were set up in 2020 (one natural history study and two therapeutic trials) targeting several neuromuscular diseases including spinal muscular atrophy, myasthenia, the autoimmune myopathies, and amyotrophic lateral sclerosis (ALS). The platform is also conducting several retrospective studies to enhance the data already acquired over the years, in adults with a variety of neuromuscular diseases.
> The Registries and databases team conducted an exhaustive collection of national data regarding patients with laminopathies in OPALE, the French observational study of laminopathies and emerinopathies. This is the largest such cohort in the world.
05 / CLINICAL CARE: SERVICE OF NEURO-MYOLOGY
> 2020 was marked by the COVID-19 health crisis, which forced the department to modify its procedures for receiving patients, to provide a safe working environment for patients and staff. Digital tools were developed, tele-consultation was introduced very quickly, and it was possible to maintain patient care. Despite the pandemic, the service has increased its use of innovative treatments, for example nusinersen for spinal muscular atrophy (SMA).
> The team of psychologists worked in close synergy with the doctors in the department, to assist patients and their families during the most acute phase of the health crisis: patient/psychologist/doctor tele-consultations were organised, psychologists provided family interventions with personalised assistance, psychiatrists provided home visits, etc. The team participated actively in the AFM-Téléthon medical/psychological assistance cell, which was put in place during the first lockdown. Therapeutic trial activity was maintained and a formalised procedure was initiated, allowing collaboration with the Trousseau Hospital team, for the transition of “Children” consultations into “Adult” consultations with a dedicated nurse.
Measures to combat diagnostic error, provided for by the Rare Diseases Plan, in particular greater use of genome sequencing, were put in place. Additionally, in the context of multidisciplinary team (MDT) meetings for “unlabelled myopathies”, the team worked at identifying patients who could benefit from high-throughput sequencing in the context of the France Genomic Medicine Plan 2025.
06 / APPOINTMENTS
> Appointment of Emmanuelle Lagrue, MD-PhD, paediatric neurologist, as joint director of the I-Motion Children clinical trial platform.
07 / DISTINCTIONS AND EVENTS
> JSFM – DAYS OF THE FRENCH SOCIETY OF MYOLOGY
Laure de Pontual, a young researcher in the Denis Furling and Geneviève Gourdon team #04 received the Institute of Myology Masters 2020 prize for her dissertation project on the identification of new factors involved in the formation of CTG repetition contractions in myotonic dystrophy type 1 (DM1).
> GRANT FROM THE FOUNDATION FOR MEDICAL RESEARCH
The study of the secretome of young and old muscle cells has earned team #03 of the Myology Research Centre, co-directed by Vincent Mouly and Capucine Trollet, a three-year grant from the Foundation for Medical Research.
This project has also been extended to the inflammatory myopathies in collaboration with team #08 headed by Olivier Benveniste via the Sanofi iAwards program.
> MARIE SKLODOWSKA-CURIE FELLOWSHIP
As a result of her preliminary work on epigenetics in mouse models, Piera Smeriglio, a postdoctoral researcher in BOND group #06 headed by Maria-Grazia Biferi, has obtained the highly prestigious Marie Skłodowska-Curie Researchers’ Individual Fellowship 2020. She is studying differences in gene regulation in spinal cord and muscle cells, in motor neuron diseases.
> ANR “YOUNG RESEARCHER” FUNDING
As a result of his preliminary work on the very precise cell mapping of the skeletal muscle, Lorenzo Giordani, a postdoctoral researcher in team #09 headed by Antoine Muchir, has obtained “young researcher” funding from the ANR (the French National Research Agency).
>25TH INTERNATIONAL CONGRESS OF THE WORLD MUSCLE SOCIETY (WMS)
This annual Congress, bringing together international muscle experts, took place virtually from 28 September to 2 October 2020.
Around 30 communications (e-posters and talks) were presented by scientific experts from the Institute of Myology, including the work of Enzo Cohen, a postdoctoral researcher in team #01 headed by Gisèle Bonne, demonstrating how he identified, in a single patient, two missense mutations, triggering a new form of myopathy.
Giorgia Querin, MD-PhD, neurologist, I-Motion Adults clinical trial platform coordinating doctor also presented his MRI study of the cervical spinal cord, to help identify early degeneration of the spinal cord in individuals not yet presenting symptoms of a disease, to predict the risk of developing a disease and to treat the disease as soon as the first symptoms appear.