Multiple Sclerosis (MS) is an inflammatory disease where the immune cells invade the central nervous system and destroy an essential element of nerve conduction: the myelin. An interesting feature observed in some patients is a regenerative process, called remyelination, which leads to the production of new myelin. However, the extent of remyelination is very heterogeneous among patients, only a minority of patients show a really efficient repair process along the disease course. In this project, our aim is to explore in vivo the biological mechanisms leading to a successful remyelination in some patients and to a failure in remyelination in others. With this purpose in mind we propose to develop a translational research platform where patients with multiple sclerosis will be investigated in vivo for their potential of remyelination through a follow-up with recently developed imaging technologies using a synergistic combination of magnetic resonance imaging (MRI) and positron emission tomography (PET) to visualize and quantify myelin and neuroinflammation. In parallel blood immune cells from patients will be sampled and profiled to investigate how they could influence remyelination. This part will consist in i) grafting patients' lymphocytes in experimental rodent models of demyelination to characterize how they could promote or inhibit remyelination; ii) performing a functional and multi-omics analysis of peripheral macrophages and analyse relationships with remyelination profiles; iii) profiling T lymphocytes at the single cell level to associate specific subpopulation of the T cells with the remyelination potential assessed in patients with MRI/PET images and in grafted animals.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
OTHER
Masking
NONE
Enrollment
80
PET-MRI: 2 at baseline visits (V0 and V1) and 1 at M6
CIC Neurosciences - Hôpital Pitié Salpêtrière
Paris, France
RECRUITINGProportion of lesional demyelinated voxels at baseline that are classified as remyelinating at month 6 of multiple sclerosis patients during the relapsing and the progressive phases of the disease
the percentage of lesional voxels classified as demyelinated on baseline \[18F\]-Florbetaben PET, that subsequently become normally myelinated on the \[18F\]-Florbetaben PET performed at 6 months, which attest remyelination
Time frame: Month 6
the percentage of voxels classified as significantly activated compared to control white matter, and the number/proportion of MS lesions classified as activated based on [18F]-DPA-714 PET
To define the individual inflammatory profiles from \[18F\]-DPA-714 PET (regional individual maps of \[18F\]-DPA-714 binding) of MS patients during the relapsing and the progressive phases of the disease
Time frame: At baseline
Proportion of each lymphocyte cluster identified from the single cell sequencing of T lymphocytes over the total T lymphocyte population for each patient
Time frame: Baseline
Remyelination level in rodents demyelinated by lysolecithin and grafted with single patient's lymphocytes quantified at week 3 post-graft
Time frame: Baseline
Proportion of lesions that persist as chronic active at month 3 post graft over the total number of lesions induced in the rodent demyelinating models by grafting patients' lymphocytes
Time frame: Baseline, at 3 Months
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