Location

Rochester, Minnesota Clinical Profile

SUMMARY

Claudia F. Lucchinetti, M.D., is a recognized international expert who investigates the clinical and neuropathological underpinnings of the broad spectrum of central nervous system (CNS) inflammatory demyelinating disorders, including multiple sclerosis (MS), neuromyelitis optica (NMO), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), acute disseminated encephalomyelitis, and Balo's concentric sclerosis.

Her laboratory relies on cutting-edge experimental neuropathological and imaging techniques, including Fourier Transmission Infrared Microscopy and X-ray-fluorescence imaging; as well as tissue-based transcriptomics and proteomics approaches to characterize tissue injury. These approaches are correlated to clinical and imaging biomarkers, including 7T in vivo as well as ex vivo imaging.

Her laboratory has been continuously funded since 2000 with support from the National MS Society, National Institute of Health and Department of Defense.

Dr. Lucchinetti's research contributions include a landmark study describing four distinct patterns of tissue damage in early active MS, suggesting that MS lesions are formed differently among different patient subgroups. This work has major clinical and therapeutic implications, and suggest that therapies should be individualized based on pathological subtype.

She was the first to propose that neuromyelitis optica was an autoimmune disease targeting a perivascular antigen. Subsequent collaborative studies confirmed the presence of a circulating pathogenic antibody against aquaporin-4 water channel, concentrated in astrocytic end feed in the perivascular space. Her foundational studies on the important role for complement-mediated injury contributed to the Mayo Clinic-led clinical trial of eculizumab, a C5a inhibitor, which became the first FDA-approved treatment for neuromyelitis optica.

Dr. Lucchinetti also led ground-breaking research describing for the first-time evidence for inflammatory cortical demyelination in early MS. She was the first to propose that MS is a disease that progresses from the outermost layers of the brain (i.e., subarachnoid space and cortex), before extending into the deeper white matter regions. This work has provided novel insights into the sequence and timing of nervous system damaging event in MS, which has led to novel imaging biomarkers of the disease, as well as a therapeutic focus on cortical damage in MS.

She authors expert content and publishes in high-impact scientific journals, which includes more than 200 peer-reviewed articles, with an h-index of 87.

Focus areas

  • Clinical, serologic, genetic, radiological and ex-vivo imaging correlates of the MS lesion
  • Pathogenic mechanisms of tissue damage across the spectrum of demyelinating diseases
  • Metal homeostasis in MS pathogenesis
  • Multimodal analysis to characterize oxidative injury in CNS demyelinating lesions, including immunopathology, synchrotron imaging, Fourier transmission infrared microscopy, proteomics and spatial transcriptomics
  • Signatures of cell stress and altered bioenergetics in MS human fibroblasts and iPSCs
  • Mechanisms of astrocyte dyshomeostasis in neuromyelitis optica
  • Clinical and immunopathological spectrum of MOGAD

Significance to patient care

Dr. Lucchinetti's research has focused on appreciating the fine structural subtleties in tissue, recognizing their clinical, pathogenic and scientific relevance, and translating these observations to clinical practice, with significant diagnostic, prognostic and treatment implications.

Her description of four distinct patterns of tissue damage in early MS has informed therapeutic response to plasma exchange for acute MS exacerbations. Her paradigm-changing research established a new understanding of lesion pathogenesis in MS, suggesting that the disease progresses from the subarachnoid space and cortex, into deeper white matter.

These observations on MS initiation and propagation have led to the development of novel neuroimaging biomarkers of the disease, and a focus on the role of the cortex in cognitive dysfunction and disease progression. Her research has defined the complex pathological substrate of MS disease progression, including the presence of smoldering slowly expanding MS lesions, as a key driver of disease progression.

Dr. Lucchinetti's pathological studies were the first to suggest the complement system plays a key role in tissue damage in neuromyelitis optica and provided the rationale for the clinical trial and subsequent approval of the first FDA-approved treatment of NMO with a complement inhibitor (eculizumab).

Professional highlights

  • Dean, Clinical and Translational Science, Mayo Clinic, 2020-present
  • Director, Center for Clinical and Translational Science (CCaTS), 2020-present
  • Board of Governors and Trustees, Mayo Clinic, 2019-present
  • Board of Directors, Mayo Collaborative Services, LLC, 2019-present
  • Council Member, National Institute of Neurological Disorders (NINDS), 2019-present
  • Eugene and Marcia Applebaum Professor of Neurosciences, 2015-present
  • Chair, Department of Neurology, Mayo Clinic Midwest, 2016-present
  • Director, American Neurological Society Board, 2018-2021
  • Robert Wartenberg Lecture Award, American Academy of Neurology, 2019
  • Board of Directors, Association of University Professors of Neurology Diversity Champion, Mayo Clinic, 2018
  • John Dystel Prize, National Multiple Sclerosis Society & American Academy of Neurology, 2016

PROFESSIONAL DETAILS

Primary Appointment

  1. Consultant, Department of Neurology
  2. Director, Center for the Clinical and Translational Science
  3. Dean, Clinical and Translational Science

Academic Rank

  1. Professor of Neurology

EDUCATION

  1. Fellow - Mayo Foundation Scholar - Mentor: Professor Hans Lassmann Institute of Experimental Neurology, Universitat of Vienna
  2. Fellow - Neuroimmunology - Mentor: Moses Rodriguez, M.D. Mayo Graduate School of Medicine, Mayo Clinic College of Medicine
  3. Resident - Neurology Mayo Graduate School of Medicine, Mayo Clinic College of Medicine
  4. Internship Rush Presbyterian St. Luke's Medical Center
  5. MD Rush Medical College
  6. Research Training - Summer Immunology Research Student - Mentor: Moses Rodriguez, M.D. Mayo Clinic in Rochester
  7. BA - Biology Northwestern University
  8. Other - Mayo Clinic Whitney MacMillan Physician Leadership Business Academy Mayo Clinic
.
BIO-00077622

Mayo Clinic Footer