Optic neuritis as a phase 2 paradigm for neuroprotection therapies of multiple sclerosis: update on current trials and perspectives

In multiple sclerosis as the most common inflammatory demyelinating disease in Western countries, major therapeutic success has been achieved with regard to strategies targeting immunological master switches. These approaches effectively reduce inflammatory disease activity but fail to address ongoing neurodegeneration or disturbed regeneration. However, intense research efforts investigating molecular mechanisms of disease have identified 'druggable' targets for prevention of inflammatory neurodegeneration and disturbed regeneration. This review covers recent developments in clinical trials using optic neuritis as a model for screening such neuroprotective and neuroregenerative therapeutic approaches.

Optic neuritis has been used in a series of recent pilot studies investigating the effects of erythropoietin, simvastatin, autologous mesenchymal stem cells, phenytoin, as well as blockade of LINGO-1 (opicinumab). Of note, these studies applied novel outcome measures related to function and structure of the visual pathway, including optical coherence tomography, full-field visual-evoked potentials, multifocal visual-evoked potential, high as well as low-contrast visual acuity. Comparison of these different approaches reveals novel insights into short-term evolution of neurobiological effects during optic neuritis and the window of opportunity for therapeutic interventions.

Translation of neuroprotective and neuroregenerative approaches to clinical reality represents a huge challenge. Optic neuritis as a prototypic autoimmune demyelinating disease offers an option for testing new therapies targeting key deleterious processes in multiple sclerosis.