Anti-Inflammatory Drugs in the Treatment of Neurodegenerative Diseases: Current State

Yossi      Gilgun-Sherki; Eldad      Melamed; Daniel      Offen

Abstract

Increasing evidence indicates that inflammation is involved in the pathogenesis of many neurological, particularly neurodegenerative diseases. Even if inflammation is not a primary causative process, its presence may contribute to the continued loss of CNS neurons. Therefore, it seems reasonable to propose that use of anti-inflammatory drugs might diminish the cumulative effects of inflammation in the brain. Indeed, some epidemiological studies performed to date, especially in Alzheimers disease, suggests that sustained use of anti-inflammatory drugs (AIDs) may prevent or slow down the progression of neurodegenerative diseases. However, small number of clinical trials carried out so far using AIDs, were minimal and equivocal in their outcome. Potential reasons for these mixed results include timing of AIDs administration, nonselective inhibition of cyclooxygenase (COX), inappropriate use of particular antiinflammatory drugs for a given disease or disease progression/ severity, sub-optimal dose in target site, or limited penetration to the brain through the blood-brain barrier (BBB). Therefore, design of AIDs for the treatment of neurodegenerative diseases based upon better BBB penetration, and with minimal adverse events, would be appropriate. In addition, relevant genetic differences among patients should be considered planning new AIDs, for improved efficacy. Furthermore, due to the possible co-involvement of oxidative stress and excitotoxicity in the pathogenesis of these diseases, combination therapy with antioxidants or glutamate antagonists or a multi-potent drug might be much more effective in successfully treating neurodegenerative diseases.

Keywords: Inflammation, Microglia, Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), Anti-inflammatory drugs (AIDs), Steroids, Non-steroid anti-inflammatory drugs (NSAIDs), Blood brain barrier (BBB)