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The invention relates to compositions comprising sulfasalazine or sulfapyridine and products of a biosynthetic pathway that requires tetrahydrobiopterin. Such compositions are useful for the treatment of inflammatory bowel diseases or rheumatoid arthritis, but without the side effects observed with sulfasalazine alone. Furthermore the invention relates to compositions comprising sulfasalazine and 5 - aminosalicylic acid (mesalamine) for the treatment of the mentioned diseases. A further aspect of the invention is a method for monitoring the progress of sulfasalazine therapy comprising measuring the tetrahydrobiopterin level in body fluids of a patient under treatment with sulfasalazine. Yet another aspect of the invention is the use of sulfasalazine or sulfapyridine in a method of preventing pain in future treatment or in disease progression, such as delaying pain in cancer patients and preventing pain in surgery, dental care, chemotherapy or radiation therapy, preventing cardiogenic shock in acute myocardial infarction, preventing brain edema formation and intracranial hypertension in traumatic brain injury, and in a method of prevention or treatment of osteoporosis. All these various aspects of the invention are based on the observation that human sepiapterin reductase is a target of sulfasalazine and its metabolite sulfapyridine.
Friedhelm Christoph Hummel, Pierre Theopistos Vassiliadis, Elena Beanato, Fabienne Windel, Emma Marie D Stiennon, Maximilian Jonas Wessel