Supported projects 

 

Each year, the EDMUS Foundation launches a call for research projects and selects research projects on multiple sclerosis using data from the French Multiple Sclerosis Observatory.

 We briefly present here some of the projects selected and supported by the Foundation.

 

Preventive use of COrticosteroids during the Post-Partum in relapsing MS patients - Laure Michel, 2018.

 

Multiple Sclerosis (MS) is most prevalent among women of childbearing age. The post-partum (PP) period is a critical phase in MS patients, during which a recrudescence of disease activity is expected. Different strategies have been assessed in the prevention of post-partum relapse. High dose methylprednisolone was evaluated in a case control study with historical controls but the positive results have not been confirmed.

 

The establishment of determinants of therapeutic lag in different forms of multiple sclerosis  - Tomáš Kalinčík, 2018

 

With an expanding number of available disease modifying therapies available in MS, personalisation of care is paramount. Therapeutic lag represents time from treatment start to its fully clinically manifest effect. Knowledge of this lag period has been dependent on pharmacodynamic drug properties, without taking individual patient and disease characteristics into account.

 

Circulation of IFN/ microRNA signatures and T cell microRNA signatures as candidate biomarkers in multiple sclerosis - Frédérique Michel , 2018  

 

Type I Interferonbis commonly prescribed as first-line therapyof relapsing-remitting multiple sclerosis (RR-MS). Yet recent studies have associated a 'type I IFN signature' with some autoimmune diseases, inflammation and chronic immune activation. It is therefore necessary to better define the boundary of the therapeutic and damaging effects of type I IFNand to investigate new disease biomarkers candidates.

 

Role of vitamin D in T cell migration - Anne Astier - project start: 2017

 

Vitamin D has known immunomodulatory unctions and vitamin D deficiency has been linked to several chronic inflammatory diseases such as multiple scleroses. Migration of activated T cells to the site of inflammation is crucial for pathogenesis. In MS, the interns VLA44 and LFA41 are key to this process. The team have shown that the bioactive form of vitamin D decreased expression and activation of VLA44, and strongly modulated the pattern of adhesion molecules expressed by activated T cells. Vitamin D similarly affected CD4+ T cells isolated from healthy controls and patients with MS. However, vitamin D promoted T cell chemotaxis, especially of CD464 Costimulated regulatory type I cell ( TR1) compared to CD284 costimulated effector T cell. Phototherapy treatment of patients with atopic dermatitis les to an increased level of circulating vitamin D and a decrease in VLA44 expression on circulating T cells but not on conventional FOXP3+ regulatory T cells (TREGS), suggesting a differential affect of vitamin D on integrin expression in vivo on effector and regulatory T cells. Overall, datas suggest that vitamin D regulates key proteins involved in the control of T cell migration, and that it favors migration of regulatory  cells over effector cells, providing novel insights into the mechanisms of the immunoregulatory role of vitamin D.

The objectivists is to correlate levels of circulating vitamin D with the phenotype of activated purified T cells in vitro in A cohort of healthy donors and untreated patients with RRMS, and assess their migratory abilities in an in vitro BBB MODEL.  

They expect donors with high levels of vitamin D to have enhanced regulatory T cells with migratory abilities coinciding with reduced migration of their effector T cells. 

 

 

Explore the pathophysiology of optic neuromyelitis - Nicolas Collongues, project start: 2017

 

The discovery of biomarkers in diseases of the optical neuromyelitis spectrum (NMOSD) has made it possible to identify several subgroups of patients with different physiopathological mechanisms.

 

NOMADMUS - French cohort of optical neuromyelitis and related disorders - Romain Marignier, project start: 2017

 

Neuromyelitis optica (NMO), is a rare but potentially devastating condition. Such as multiple sclerosis (MS), NMO is an inflammatory auto-immune disorder of the central nervous system. Since the end of the past century, NMO was considered as a subtype of MS until the 2004 discovery of a specific antibody, aquaporin4-IgG (AQP4-IgG), which enabled the distinction between these two diseases. Detecting this autoantibody led to the extended concept of NMO spectrum disorders (NMOSD) that encompasses now also patients with auto-antibody against the myelin oligodendrocyte glycoprotein (MOG), and without any autoantibodies (double seronegative). Among other international efforts, the launch in 2009 of a national French cohort on NMO and related disorders, NOMADMUS, led to a quantum leap in NMO knowledge and management.

 

Action-MS - Effect of early treatment on disability progression in multiple sclerosis: an observational study of the OFSEP database - Emmanuelle Leray, project start: 2017

 

Treatment options for Relapsing-Remitting Multiple Sclerosis (RRMS) largely evolved for the last twenty years. Natural history studies, immunopathological studies and extensions of randomized clinical trials incite to act soon in disease development. Some observational studies tend to show a greater benefit of early treatment initiation on disability progression. Nevertheless, the benefit of early action remains to be confirmed by rigorous observational studies taking into account both MRI and clinical data.

 

Atypical Multiple Sclerosis. A multicentric study - Pierre Labauge, project start: 2016

 

This study was published in 2019

MS criteria are well known, based on Mcdonald criteria 2010. MAGNIMS group (2016) proposed new MS ctriteria. MS diagnosis is based on  inflammatory central nervous system (CNS)  involvement (clinical relapses, inflammatory reaction on CSF study and inflammatory lesions on MR exam). Some inflammatory CNS diseases are more and more recognized, but without fulfilling MS criteria. 

 

SURVIMUS II - Net survival in multiple sclerosis patients in France - Emmanuelle Leray, project start: 2016

 

Net survival is defined as the survival which might occur if all risks of dying from other causes than the disease of interest, here multiple sclerosis (MS), were removed. It is estimated from “excess mortality” that isobtained as the difference between the overall mortality observed in the MS population and the overall expected mortality in the general population. The advantage of this approach, which does not require the information about the cause of death, is to take into account mortality indirectly related to MS, which cannot be achieved in the cause- specific setting.

 

Implementation of a pregnancy register included in the OFSEP cohort - Sandra Vukusic, project start: 2016

 

The influence of pregnancy on the course of multiple sclerosis (MS) has long been a controversial topic. After the publication of the first large prospective study of pregnancy and MS in 1998, counselling of women with MS has radically changed and many patients have been able to fulfil their desire of motherhood. However, there are still some challenges for the neurologist, who has to face old unanswered questions or new issues, regarding the use of disease modifying drugs (DMDs) in this period of life, effects on the short and long term outcome of the mother (in terms of relapses and disability) and the child, role of breast-feeding and locoregional analgesia.