Johns Hopkins Center for NMO, Recurrent TM, and Related Neuroimmunologic Disorders
Clinical Care and Research
Michael Levy MD PHD

I have established a new center at Johns Hopkins.  My clinical focus is on Neuromyelitis optica (NMO), longitudinally extensive Transverse Myelitis (TM), recurrent TM, bilateral optic neuritis and recurrent optic neuritis.  Appointments at my clinic can be made by calling Mary Brown at (410)502-7099.

Neuromyelitis optica (NMO) is a devastating neuroinflammatory disorder targeting the optic nerves and spinal cord leading to blindness and paralysis.  The cause of the disease is unknown, but the recent discovery of a serologic antibody against aquaporin-4 (AQP4) in patients with NMO implicates AQP4 as a key player in pathogenesis.  AQP4 is the predominate water channel in the brain expressed on the foot processes of astrocytes around blood vessels where it may be important in regulating the permeability of the blood brain barrier (BBB).  In humans, there are two isoforms of AQP4.  The shorter AQP4 variant, M23, forms organized orthogonal arrays of membrane channels that maintain BBB integrity.  In contrast, the longer variant of AQP4, M1, disrupts M23 arrays and destabilizes the BBB.  Loss of BBB integrity in NMO patients may permit the influx of humoral immune mediators, including IgG, IgM and complement factors that characterize the pathology of NMO lesions.

The objective of our lab is to understand exactly how AQP4 isoforms are involved in inflammation of the optic nerve and spinal cord of NMO patients. The hypothesis is that an imbalanced expression of AQP4 isoforms (M1 and M23) creates regions in the central nervous system (CNS) that are more susceptible to inflammation in NMO.  Our first aim is to understand why NMO inflammation is largely confined to the optic nerve and spinal cord and how AQP4 isoforms confer susceptibility to inflammation.  In addition, we are looking at functional effects of inflammation on AQP4 isoforms using cell cultures of human astrocytes exposed to humoral inflammatory mediators.  Based on the findings from these experiments, rodent models of NMO will be developed with an imbalance of M1 and M23 to recreate the susceptibility to CNS inflammation.

Since Dr. Eugène Devic first described NMO in 1894, neurologists have been puzzled about the localization of disease to the optic nerve and spinal cord.  Our research not only seeks to explain the unique susceptibility of inflammation to the optic nerve and spinal cord, but also delves into the mechanism of disease to yield new information about how AQP4, and the individual AQP4 isoforms, are involved in NMO.  Development of an animal model of NMO based on differential AQP4 isoform expression will significantly improve our understanding of the pathogenesis and move the field toward finding new targets for therapy.