New treatments in neuroinflammatory disorders

Abstract

The understanding of how to treat neuroinflammatory disorders is dependent upon a clear understanding of the mechanisms of disease, which are only recently becoming clear. One of the most significant advances has been discovery of autoantibody biomarkers which define treatable autoimmune encephalitis and autoimmune demyelination syndromes such as autoantibodies against NMDA-receptor, myelin oligodendrocyte glycoprotein and aquaporin-4. Although corticosteroids remain an essential part of early treatment as they reduce inflammation quickly, the therapeutic options are increasing due to our improved understanding of disease. Intravenous immunoglobulin is a useful anti-inflammatory therapy, although its mechanisms is broad, and its effects may vary from disease to disease. Plasma exchange is more stratght forward, as it removes pathogenic autoantibodies and other inflammatory proteins. Therapies which target B cell linage such as rituximab are increasingly used in autoimmune neurology, and there is recent scientific data showing that targeting CD20 B cells can be therapeutically effective in autoantibody syndromes. Recent understanding that complement plays a major role in aquaporin-4 NMOSD has resulted in the use of complement targting drugs such as eculizumab. Likewise, tocilizumab which targets interleukin 6 is an increasingly interesting option in autoimmune encephalitis patients who fail rituximab, and other neuroinflammatory disodrers which are not ‘autoantibody mediated’. Neuroinflammation can take other forms, and there is increasing interest in epigenetic immune dysfunction, and therefore the use of epigenetic therapeutics, which opens up the potential opportunity of repurposong drugs which are epigenetic modulators such as ketogenic diet, cannabidiol, and valproate, amongst many.