Review of laquinimod and its therapeutic potential in multiple sclerosis.
BACKGROUND
Multiple sclerosis (MS) is a chronic immunological disease of the central nervous system characterized by early inflammatory demyelination and subsequent neurodegeneration. Although major progress has occurred, MS is still an incurable disease. Further, parenteral application and/or safety issues of the currently licensed drugs are associated with low patient compliance. Thus, there remains an unmet need for the development of more effective and well-tolerated oral therapies for the treatment of MS. At this point in time, different oral available substances are under investigation and hold promise in the treatment of relapsing-remitting MS (RRMS).


METHODS
The physical, chemical and pharmacological properties of laquinimod , as well as its suggested mechanisms of action, clinical efficacy and side-effect profile are reviewed.


CONCLUSIONS
Laquinimod is a new orally administered synthetic drug designed as an immunomodulator. Its mechanisms of action are not yet fully elucidated. Studies in mice and humans revealed different mechanisms of action, including anti-inflammatory and neuroprotective effects. So far, Phase II and Phase III clinical trials have shown its efficacy on magnetic resonance imaging based measures of disease activity, annualized relapse rate and disability progression in RRMS patients. Current data suggest a relatively modest efficacy by measures of relapse rate and there seems to be no superiority in comparison to established disease-modifying agents in relapsing-remitting MS. Further studies are necessary to evaluate both neuroprotective efficacy and optimal dosage of laquinimod in more detail.
Ruhr-University Bochum, Department of Neurology at St. Josef-Hospital Bochum , Gudrunstr. 56, D-44791 Bochum , Germany +49 234 509 2411 ; +49 234 509 2414 ; ralf.gold@rub.de.
Jan
J
Thöne
Ralf
R
Gold
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D006801:Humans; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015363:Quinolones / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*
D000893:Anti-Inflammatory Agents; D018696:Neuroprotective Agents; D015363:Quinolones; C476223:laquinimod; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human