Claudia Lucchinetti, MD
Dr. Lucchinetti's area of research interest is on investigating the immunopathology and pathogenesis of multiple sclerosis, neuromyelitis optica and other CNS inflammatory demyelinating disorders. Her laboratory uses experimental neuropathological techniques in order to investigate the mechanisms of tissue damage across the spectrum of demyelinating diseases. Her work has suggested there is interindividual pathogenic heterogeneity in MS and she is principal investigator of the MS Lesion Project, an international collaborative study investigating the clinical, serologic, genetic and radiological correlates of the MS lesion. She has clinically and radiographically characterized the largest cohort of patients presenting with large, tumefactive demyelinating lesions, and determined the majority develop typical MS, with a clinical course and disability profile similar to prototypic MS. She has determined that cortical demyelination is an important pathological substrate of disease progression in MS, and begins early in the disease process. She is currently investigating the role of early cortical demyelination in perpetuating autoimmunity in MS. Dr. Lucchinetti described the unique pathological features of NMO, characterized by vasculocentric immune complex deposition, and she proposed NMO was an autoimmune disease targeting a perivascular antigen. Subsequent studies led by Dr. Vanda Lennon and the Mayo NMO consortium identified a highly specific and sensitive serological biomaker,NMO-IgG which specifically targets the aquaporin-4 water channel, concentrated in astrocytic end-feet in the perivascular space. Dr. Lucchinetti demonstrated that the normal distribution of aquaporin-4 corresponded to the pattern of complement activation described in NMO lesions, and showed that NMO lesions were characterized by a striking loss of AQP4, suggesting NMO-IgG was a pathogenic autoantibody. In collaboration with Drs. Charles Howe and Hirohito Kita, she is using pathological, in vitro, and experimental animal model studies to investigate the synergistic relationship between astrocytes, eosinophils, and NMO-IgG in disease pathogenesis. Dr. Luccchinetti has also characterized the clinical, radiographic, and pathological features of acute disseminated encephalomyelitis and described a novel pattern of cortical microglial inflammation in ADEM, thought to represent the pathologic substrate of encephalopathy in this disorder. Dr. Lucchinetti is active in clinical and basic science research and is a member of the Center for Multiple Sclerosis and CNS Demyelinating Diseases, as well as the Mayo NMO Consortium. She has extramural funding from the National MS Society, the National Institute of Health, and the Guthy-Jackson Charitable Foundation.
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