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Paraneoplastic Neurologic Degeneration

The paraneoplastic neurologic disorders (PNDs) are a set of neurodegenerative disorders that arise in the setting of cancer and are believed to be immune mediated (reviewed in Darnell RB and Posner JB. N Engl J Med, 349:1543-1554, 2003 and Darnell RB. Arch Neurol, 61:30-32; 2004). PND patients harbor high titer autoantibodies targeted to specific tumor and neuronal antigens (termed onconeural antigens). We have used PND antisera to clone and characterize the target antigens.

The significance of the PNDs is several-fold. The disorders are associated with tumor immune responses that are effective, as well as autoimmune neurologic disease, both issues of major clinical importance. In addition, it is believed that the onconeural antigens are immunogenic in part because of their tissue restriction-the proteins appear to be expressed normally only in immune privileged neurons (and in some instances testes), and abnormally in specific types of tumor cells. The study of their biology is relevant to the areas of neuroscience (Musunuru K and Darnell RB. Annu Rev Neurosci, 24:239-62, 2001) and cancer biology (Albert ML and Darnell RB. Nature Rev Cancer, 4:36-44, 2004). We are actively studying the biology of two PND antigens that are neuron-specific RNA binding proteins, the Nova and Hu antigens.