Members of the Inhibitor of Apoptosis (IAPs) Family as Markers of Disease Subtype and Treatment Response in Multiple Sclerosis

Multiple sclerosis (MS) is a progressive neurological disorder characterized by an autoimmune mediated attack against the myelin sheath of a neuronal axon. MS is the most common non-traumatic disorder of the central nervous system (CNS) in young adults. The clinical course of MS has been divided into four major categories: relapsing-remitting (RR), secondary-progressive, primary progressive and benign. Patients with benign forms of MS show little or no progression after their initial attack and require no therapeutic intervention. However, early identification and treatment of more aggressive forms of MS slows disease progression. IFN-b is a very expensive therapy ($17,000 per year) and benefits are modest while some RR MS patients do not respond to IFN-b. At the current time, there are no diagnostic tests that enable a clinician to predict the likelihood of a RR patient responding to IFN-b. Members of the Inhibitor of Apoptosis (IAPs) family of genes may form the basis of diagnostic tests predictive of IFN-b responsiveness. It is hypothesized that XIAP and HIAP-1 levels will predict disease severity while XAF-1 levels will be predictive of IFN-b responsiveness. The present proposal has the potential to produce new tools that would not only improve the clinical management of MS but may serve as surrogate markers for biochemical efficacy of new MS therapeutics.