Laquinimod is rapidly absorbed following oral administration with bioavailability of 82%-95%. Two Phase 2 clinical trials were conducted with laquinimod. Both demonstrated a reduction in the frequency of gadolinium (Gd)-enhancing lesions and relapses in patients with relapsing-remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS). Laquinimod was well tolerated in both Phase 2 trials with few side effects. There was no difference in the overall number of adverse events (AEs) or serious adverse events (SAEs) between the placebo and laquinimod groups. Laquinimod effectively ameliorates both acute and chronic experimental autoimmune encephalomyelitis (EAE) decreasing both demyleination and axonal loss. Laquinimod may have protective effects on axonal integrity beyond that associated with decreased inflammation. Laquinimod has no immuno suppressive effects in animal models or in human studies, and does not decrease the ability of animals to mount a cellular or humeral immune response. The safety profile of laquinimod appears quite favorable.

In acute multiple sclerosis (MS) lesions, axonal pathology and the number of transected axons correlate with the number of immune cells and therefore with inflammatory activity. In addition to the commonly described white matter locations, demyelination also occurs in the gray matter of MS patients. The concept of MS as an inflammatory demyelinating and neurodegenerative disease provides a framework to help explain disease progression and development of permanent neurological disability in MS patients. Prevention of persistent neurological disability is the main goal when treating neurological diseases. In contrast to most neurodegenerative diseases, patients with MS can be identified early before the occurrence of extensive neurodegeneration by the presentation of symptoms mediated by inflammatory demyelination. Therefore, neuroprotective therapeutics may have a greater probability of clinical efficacy in MS patients since treatment can be initiated before extensive axonal loss. Regardless of the cause of MS, axons and neurons are important therapeutic targets.

This chapter reviews the mechanisms for both inflammatory and non-inflammatory mediated neural degeneration in multiple sclerosis (MS) and discusses potential therapeutic targets for neuroprotection. The classical pathological description of the MS lesion has focused on the perivenular inflammatory infiltrate characterized predominantly by lymphocytes and monocytes. Progressive axonal loss occurs in the central nervous system (CNS) of patients with MS, and the extent of this axonal loss correlates with the degree of permanent neurological deficit. Careful consideration to the pathophysiology of MS is necessary to identify candidate drugs for therapeutic trials. Stem cells may serve to enhance the function of host tissues, to provide missing chemicals or enzymes or to halt a degenerative or neoplastic process. As the currently available immunomodulatory treatments for MS have only a modest impact on progressive axonal loss and disability, there exists a pressing need to develop strategies to prevent this axonal loss.