Multiple sclerosis: a current overview of failed and interrupted treatment trials

Immunobiological findings together with advances in biotechnology, ameliorations in clinical trial design,and MRI developments have led to a variety of therapeutical approaches in multiple sclerosis (MS). However, in contrast to successfully introduced new treatments, a number of therapeutical failures exist as well: despite impressive data from animal models, convincing concepts, and promising phase MRI studies, some investigated drugs and strategies showed no positive effects in clinical trials, or trials had to be terminated because of unexpected side effects. This article provides an overview of clinical studies that have failed or been abandoned for other reasons. Tumor necrosis factor (TNF) alpha-antagonists which have led to negative effects in two studies (Lenercept, Infliximab) are discussed in detail. These results raise critical questions concerning the hypothetical pathogenesis of MS lesions a nd the value of MRI in the assessment of clinically relevant therapeutic drug effects. In addition to a description of the immunobiological background, studies on the immunosuppressive agents linomide, deoxyspergualin, sulfasalazine and cladribine, trials for the cytokines interleukin-10 and TGF-beta 2, the studies on remyelination by intravenous immunoglobulins (IVIg), oral tolerance, and extracorporeal photopheresis are discussed.