The aim of the MoCoDev project is to implement a new model of human cortical development. This model will allow quantitative characterisation of the complex changes observed in the shape of the cortex from a simple and smooth surface in the early stages of development to the highly folded adult brain. In the first work package, we will introduce new descriptors of cortical geometry that can be extracted from anatomical MRI, with particular emphasis on the dynamics of cortical folding. We will develop specific measures that allow us to track the spatio-temporal evolution of the folding patterns and incorporate these measures into our model. In the second work package, we will apply our model to two specific populations with abnormal early brain development (corpus callosum agenesis and preterm birth), allowing us to assess potential relationships between folding patterns and underlying structural connectivity. Ultimately, our model will be instrumental in detecting cortical malformations early in development. It will also contribute to a better understanding of the biological rules governing the development of complex cortical geometry and its links to the functional organisation of the brain.

In 2013, the pill scare in France has underlined the need for identifying at risk women before the first prescription of combined Oral Contraceptive (COC) to prevent the potentially life-threatening risk of Venous Thromboembolism (VTE). However, no efficient and powerful tool is currently available to achieve this goal. We have developed a clinico-biological prediction score whose performance is encouraging. However, it needs to be improved before it can be used in clinical practice. Capitalizing on unique preliminary genomic data already obtained and 2 case-control studies specifically designed to identify biomarkers for COC-induced VTE (PILGRIM and PILGRIM2), the ROSA-VT project has 3 objectives: (i) Improvement of the PILGRIM score by including new genetic variants obtained by different strategies already implemented by our teams; (ii) Identification of a proteomic signature of the risk of VTE in COC users; (iii); Derivate and validate a new clinic-biological score based on the new biomarkers identified through objectives I to II to predict the risk of VTE on COC in clinical practice. The ROSA-VT intends to solve a public health issue. The information generated will contribute to improve the prediction of VTE occurrence in COC users by identifying and validating new biomarkers (proteomic and genetic). It will also allow the development of a dedicated VTE risk score for women on COCs and has considerable potential for prevention in women before contraception is prescribed. This targeted preventive strategy, based on the choice of the appropriate type of contraception according to the score, will decrease the incidence rate of VTE in women of childbearing age. Early detection of women at risk to prevent the onset of the disease will improve patient care and quality of life, avoiding both overmedicalization and nonessential interventions.

Epilepsy, a chronic neurological disorder affecting millions worldwide, necessitates innovative diagnostic and treatment approaches. In this context, sound-based interventions stand as a non-invasive and patient-friendly complement to traditional methods. Nevertheless, the potential impact of sound on this condition remains insufficiently explored, representing a missed opportunity for improvement. This grant proposal aims to fill this gap by exploring the transformative possibilities of sound-to-brain mapping within epilepsy research, with the goal of reshaping both diagnostic procedures and treatment options. While it is well-established that auditory emotions can influence seizure occurrence, the intricate interplay between sound, emotions, and epilepsy has been underinvestigated. This research initiative holds two primary objectives: firstly, to investigate epilepsy by harnessing sound's capability to modulate neuronal excitability, thus shedding light on diagnostic enhancements. Secondly, to explore the therapeutic potential of complex musical sequences for seizure control. This multidisciplinary approach combines aspects of affective neuroscience, music science, and neurotechnology, promising innovative solutions for epilepsy management. By integrating emotional assessments, objective physiological measurements, and cutting-edge EEG tools, we aim to not only improve our comprehension of epilepsy but also to develop home-based solutions for diagnosis, patient follow-up, intervention, and lay the foundation for future clinical trials using portable EEGs, ultimately translating these advancements to the patients.

Multiple Sclerosis (MS) affects between 70.000 and 90.000 persons in France, with females outnumbering males in a 1.7:1 ratio. The disease onset is mainly around 30 years old – hence MS is the first cause of non traumatic disability in the young adult. MS is a chronic inflammatory disease of the central nervous system leading to demyelination and axonal degeneration. When myelin is destroyed, it leaves random areas of scar tissue (sclerosis) which affect the ability of nerve cells to communicate with each other and results in the blocking of neurological transmissions leading to physical and cognitive disability. It is now commonly admitted that MS is not only an inflammatory disease but a neurodegenerative disease as well. Indeed the repeated assaults suffered by the neurons and their supportive cells, especially the myelin producing cells: the oligodendrocytes, lead to the premature death of these two cell types, this death resulting in progressive loss of function in the patient. After promising preliminary results obtained in 2007, Trophos (Partner 1) along with the IBDML (UMR 6216) and CRMBM (UMR 6612) explored from 2008 to 2011 the activity of the molecule olesoxime in various in vitro and in vivo models of MS (MS-Repair ANR, ANR-08-BIOT-016-01). This project showed that the molecule is not only neuroprotective, but it has the ability to promote the maturation of oligodendrocyte progenitor cells (OPCs) into myelinating oligodendrocytes. However, before considering a large-scale clinical trial to assess efficacy, we must first check compatibility of olesoxime with existing treatments, the most frequent being interferon beta1. A second important aspect is that to date, no treatment for neuroprotection / remyelination has reached the stage of clinical proof of concept that aims Trophos. Lacking of predefined path and after discussion with MS experts, it appears that the best criteria for assessing neuroprotective/remyelinating effect of the drug candidate, are MRI criteria. However, these imaging criteria have not yet been validated for use in multicentre trials - so we must also check the feasibility of such measures under this condition. This goal can be achieved through the expertise of partner AP-HM/CNRS-CEMEREM-CRMBM (Partners 2 and 5), along with the collaboration of CHU de Rennes and CHU de Reims (Partners 3 and 4). The Translate-MS-Repair project presents a double innovation: Therapeutic innovation (driven by Trophos): There are currently no registered treatment on the market for neuroprotection / remyelination in MS - arrival on the market of such a product would be a major therapeutic innovation in the medical management of the disease. Methodological innovation (driven by the APHM / CNRS-CEMEREM-CRMBM): The relative youth of the concept of neuroprotection / remyelination makes that there was no large scale clinical research performed to date to demonstrate the effectiveness of a drug candidate in this area. The path remains to be drawn with tools and methodology not defined yet. Such tolls and methofdology therefore require a validation in a multicenter context. Demonstrating the feasibility of a consistent measures of neuroprotection / remyelination will not only allow the further development of olesoxime, but it will also be a reference for future development of products with the same therapeutic concept.