Identification of inflammatory neuronal injury and prevention of neuronal damage in multiple sclerosis: hope for novel therapies?

IMPORTANCE: Although multiple sclerosis (MS) has long been considered the prototype for an inflammatory, demyelinating disease of the central nervous system, modern histopathology and imaging techniques show that significant damage to neuronal structures already start occurring in the earliest stages of the disease. As the disease progresses, the extent of neuronal pathology accumulates. Therapeutic progress in terms of the prevention of increased disability has only just begun.

OBJECTIVE: To review possible diagnostic improvements of neuronal compartment pathology as well as direct therapeutic interventions based on reports from the last decade and outline clinical results from studies and perspectives on the progression of MS.

EVIDENCE REVIEW: Literature search focused on publications and the references contained therein, relating to neuronal compartment pathology and direct therapeutic interventions published in the last decade in well-established peer-reviewed journals. The quality of the cited works was ensured by their acceptance by peer review, participation in clinical trials, and authors' own expert assessment.

FINDINGS: Current MS therapies as well as medications that are in late phase 3 trials or under approval exhibit primarily anti-inflammatory properties. However, clinical and imaging data demonstrate the potential of using novel therapies to prevent neuronal damage. Whether these exhibit effects on the neuronal compartment due to interference with the immune system or additional direct effects depends without question on the specific mechanism of action.

CONCLUSIONS AND RELEVANCE: Combining anti-inflammatory and direct neuroprotective, neuroregenerative/repair therapy strategies may open up new avenues in the treatment of MS.