Anti-inflammatory strategies for the treatment of multiple sclerosis – tryptophan catabolites may hold the key

Breakdown of the essential amino acid tryptophan by indoleamine-2,3-dioxygenase has profound suppressive effects on T cell immunity. These immunosuppressive effects are in part mediated by natural tryptophan catabolites (kynurenines), including anthranilic acid and quinolinic acid derivatives. The synthetic, orally active anthranilic acid derivative tranilast ameliorates the disease severity of experimental autoimmune encephalomyelitis. Orally active quinoline derivatives such as teriflunomide and laquinimod displaying similar T cell suppressive effects are currently undergoing clinical trials for the treatment of multiple sclerosis. Synthetic kynurenines may define a new class of anti-inflammatory drugs for the treatment of TH1-mediated autoimmune disorders including multiple sclerosis.

Section editor:Martin Braddock – AstraZeneca R&D Charnwood, Loughborough, UK