Neuromyelitis Optica (NMO) Variant of Multiple Sclerosis

Neuromyelitis optica (NMO), also known as Devic's disease, is a recurrent inflammatory demyelinating disease that affects optic nerves and the spinal cord, with potentially devastating consequences in some patients.

Neuromyelitis optica accounts for 10 to 60 percent of cases of multiple sclerosis (MS)-like illness in Asia. In North America, although the majority of affected individuals are Caucasian, NMO disproportionately affects non-Caucasians.

NMO is occasionally misdiagnosed as MS, but treatments effective for MS are often ineffective or even harmful for neuromyelitis optica.

Mayo Clinic is recognized as a center of excellence for NMO diagnosis, treatment and research. The NMO Study Group encompasses neurologists and bench scientists at all three Mayo campuses with a focused commitment to discover the cause of this disease and to develop new and better treatment strategies. Because of major advances in the understanding of the pathogenesis and the genetic basis of NMO, a cure is foreseeable for NMO (the most severe form of MS) likely before any other form of CNS inflammatory demyelinating disease.

Discovery of the first antibody marker specific for NMO and its reporting in 2004 was a major breakthrough for Mayo's NMO study group. In just three years this antibody test has enabled accurate diagnosis and therapy of MS and related diseases nationally and internationally. A positive result for the NMO-IgG antibody allows early distinction of NMO from MS, and thus early initiation of NMO-appropriate treatment. The close collaboration between all members of the NMO Group exemplifies Mayo's multidisciplinary team approach to clinical problems. Clinical outreach via antibody testing performed in the Neuroimmunology Laboratory (Drs. Lennon and Pittock) on behalf of the Department of Laboratory Medicine and Pathology (40,000 patients annually), currently identifies approximately 70 NMO-IgG positive patients every month.

This resource serves as a conduit for patient recruitment to clinical trials. Neuropathological research (Lucchinetti laboratory) contributes further value to this outreach practice by providing unique insights into the immune mechanisms causing NMO through the analyses of tissues obtained form NMO patients. Dr. Lucchinetti is also investigating tissues from animals with experimentally-induced NMO in an effort to correlate our clinical observations with a model system that is amenable to genetic and pharmacological manipulation. Likewise, Dr. Howe is developing in vitro cell-based models of the neuro-immune interface that will permit mechanistic investigations of NMO immunopathology at the cellular and molecular level. Finally, two of the NMO Study Group's clinical neurologists are world-renowned for their expertise in the epidemiology (Wingerchuk) and genetics (Weinshenker) of NMO and all members of the NMO study group have exceptional expertise in the accurate diagnosis and optimal management of patients with NMO, and in the design and conduct of therapeutic trials.

The complementary talents and subspecialty interests of this coalition of Mayo clinicians and scientists reflects a long history of working together on projects related to multiple sclerosis. The NMO projects have attained critical momentum in the past 18 months.

Highest priority goals are to:

  1. Establish animal models of NMO to allow development and preclinical testing of more specific immunotherapies (Drs. Lennon, Howe, Lucchinetti)
  2. Initiate therapeutic trials with emerging immunomodulatory agents that have not been tested in NMO (Drs. Pittock, Weinshenker, Wingerchuk, Lucchinetti)
  3. Investigate the natural history of NMO and its spectrum of related disorders (Drs. Pittock, Weinshenker, Wingerchuk, Lucchinetti)
  4. Investigate genetic determinants of NMO (Weinshenker)
  5. Investigate the mechanisms of demyelination and tissue injury in NMO and emerging experimental in vivo and in vitro models. (Drs. Lucchinetti, Howe and Lennon)
  6. Develop and validate novel functional assay systems for quantitative detection of pathogenic subpopulations of NMO-IgG and investigate the potential correlation of serum levels of each antibody with the individual patient's disease severity and course. (Drs. Pittock and Lennon)