A Phase I/II clinical study of an innovative neuroprotective and remyelinating compound in Multiple Sclerosis patients: translational phase of the MS-Repair project. – Translate-MS-Repair

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.