Funding Methods

Our method of funding derives from our mission to fund biomedical research specific to Neuromyelitis Optica (NMO) Spectrum Disease. We are committed to enhancing the knowledge base of NMO by funding innovative research approaches for studying and advancing the understanding of the pathophysiology and biochemistry of NMO.

In the United States, our funding is focused on, but not limited to researchers who are affiliated with U.S. 501(c)(3) or other tax-exempt organizations. The Guthy-Jackson Charitable Foundation does not fund individuals who do not meet our funding criteria and eligibility.

There is currently no open call for funding opportunities for research.

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Currently Funded Research Sites

Mayo Clinic

Principal Investigator: Dr. Vanda Lennon
Project Title: Development and Validation of Aquaporin Autoimmunity Models

Principal Investigator: Dr. Brian Weinshenker
Project Title: Genetics of Neuromyelitis Optica and Molecular Basis of Susceptibility

Principal Investigator: Dr. Sean Pittock
Project Title: Bench to Bedside Investigation of Aquaporin (AQP4) Autoimmunity:Epidemiology and Translation

Neuromyelitis optica (NMO) is a devastating and poorly understood inflammatory demyelinating disease of the central nervous system that resembles multiple sclerosis but has several distinctive characteristics. These differences convinced Mayo Clinic investigators that detailed study of NMO from a fresh perspective might bring new insights to the entire field of multiple sclerosis-like diseases. The Mayo NMO Consortium has coalesced over the past decade as an interactive team of clinical and basic investigators with a common interest in neurological autoimmunity and neuroprotection. The complementary expertise of our consortium (clinical, pathological, immunological, epidemiological and genetic) has spawned a coordinated effort to understand NMO. The goals of the Mayo NMO Consortium are to:

• Uncover the genetic and biological factors that lead to development of NMO
  
  
• Define the pathophysiologic mechanisms that are unique to NMO
  
  
• Produce animal models of the disease
  
  
• Develop novel and specific therapeutics based on our discoveries in pathophysiology

The consortium is developing a central repository of NMO patient-derived data and biospecimens as the basis for future and ongoing research with national and international collaborators. Infrastructure provided by the Guthy-Jackson Foundation facilitates integration of clinical and basic research activities, including development of novel antibody tests for early identification of and prediction of the course of disease, development of authentic animal models to explore new therapeutic approaches and design of clinical trials to test the efficacy of new therapies.

The Mayo Team members:

• Charles L. Howe, Ph.D., Assistant Professor of Neurology and Neuroscience, Mayo Clinic College of Medicine

• Vanda A. Lennon, M.D., Ph.D., Professor of Immunology and Neurology, Mayo Clinic College of Medicine
  
  
• Claudia F. Lucchinetti, M.D., Professor of Neurology, Mayo Clinic College of Medicine

• Sean J. Pittock, M.D., Associate Professor of Neurology, Mayo Clinic College of Medicine

• Brian G. Weinshenker, M.D., Professor of Neurology, Mayo Clinic College of Medicine

• Dean M. Wingerchuk , M.D., Professor of Neurology, Mayo Clinic College of Medicine

Website: http://www.mayoclinic.org/devics-disease/diagnosis.html

• The Guthy-Jackson Charitable Foundation congratulates Dr. Marcelo Matiello at the Mayo Clinic for receiving the Mayo Clinic Neurology Research Award for research on the genetics of NMO.
  

 

Stanford University

Principal Investigator: Dr. Lawrence Steinman
Project Title: Proteomic Studies Leading to Development of Tolerizing Therapy in NMO

The Stanford team has pioneered the development of technologies to study the proteins, lipids and genes expressed in brain tissue from individuals with demyelinating diseases like multiple sclerosis, adenoleukodystrophy and acute disseminated encephalomyelitis. Their custom made arrays have illuminated the broad range of antibodies in the blood and spinal fluid in various demyelinating conditions. These antibodies are directed to the proteins and lipids of the myelin sheath, to other glia, and to neurons. Some of the most abundant antibodies target molecules that protect the brain and spinal cord from damage, thus attacking the guardian molecules that actually serve to protect the brain. The studies funded by the Foundation in NMO will now enable the group to translate these results into a potent new and highly specific therapy for NMO. The Stanford group has been already been successful in translating their research into new therapies for demyelinating disease. Their research during the early 1990’s lead to the discovery of Tysabri, the most potent approved drug for MS. The long range aim of the Stanford team is to develop a powerful, safe, specific tolerizing immune therapy aimed at eliminating the main immune responses in neuromyelitis optica, while leaving the rest of the immune system intact. Elimination of these pathological immune responses directed to the optic nerve and spinal cord should help arrest the disease.

The Stanford University NMO Team

• May Han, MD Senior Fellow in Neuroimmunology; Acting Assistant Professor of Neurology and Neurological Sciences
  
  
• William R. Robinson, MD PhD Assistant Professor of Medicine
  
  
• Lawrence Steinman, MD George A. Zimmerman Prof. of Neurology, Pediatrics and Genetics, Chair Interdepartmental Program in Immunology

Website: http://steinmanlab.stanford.edu/

 

University of California, San Francisco - Verkman Laboratory

Principal Investigator: Dr. Alan Verkman
Project Title: Role of AQP4 Autoantibody in Neuromyelitis Optica

The research will address basic questions about the role of AQP4 autoantibodies in NMO at the AQP4 molecular level, astrocyte cell level and whole organism level. In the first aim, biophysical methods developed in the lab will define the AQP4 isoforms that bind NMO-IgG, and the effect of NMO-IgG on AQP4 function, assembly and processing. Possible effects of NMO-IgG on AQP4 water permeability and supermolecular assembly will be investigated. The second aim will use cell culture models to investigate the role of NMO-IgG on key astrocyte functions such as cell migration and vesicular trafficking. The third aim will use mouse models to address key questions in NMO pathognesis, such as: Does NMO-IgG cause NMO? Why does NMO-IgG damage the central nervous system, but spares AQP4-expressing peripheral organs? How does NMO-IgG cause demyelination? The lab will also attempt to create mouse models of NMO by passive transfer of NMO-IgG using AQP4 null mice as a key control.

UCSF, Verkman Lab Team

• Alan S. Verkman, M.D. Ph.D., Professor of Medicine and Physiology, UCSF
  
  
• Marios C. Papadopoulos, M.D. FRCS(SN), Senior Lecturer in Neurosurgery, St. George's, University of London (co-principal investigator
  
  
• Jonathan Crane, Ph.D., Post-doctoral Fellow, UCSF
  
  
• Lukmanee Tradtrantip, Ph.D., Post-doctoral Fellow, UCSF
  
  
• Samira Saadoun, Ph.D., Post-doctoral Fellow, St. George's, University of London
  
  
• Hua Zhang, Ph.D., Post-doctoral Fellow, UCSF
  
  

Website: http://nephrology.medicine.ucsf.edu/verklab/

 

University of California, San Francisco - Zamvil Laboratory

Principal Investigator: Dr. Scott Zamvil
Project Title: Tcell Recognition of Aquaporin-4 in Neuromyelitis Optica

Autoantibodies directed against aquaporin 4 (AQP4), the primary candidate autoantigen in neuromyelitis optica (NMO), are detected in a high percentage of NMO patients. These AQP4-specific antibodies are IgG1, a subclass of mature IgG that requires help from CD4+ T cells. However, little is known regarding the T cells that react to AQP4. To further understand the role of AQP4 in NMO, it is critical to characterize how T cells recognize this protein. The Zamvil Lab hypothesizes that AQP4-specific T cells may be activated and/or expanded in NMO patients. In this research program, they will identify and characterize the determinants of AQP4 that are recognized by T cells in NMO patients using cells derived from blood samples. In addition, an animal model of NMO would be advantageous for understanding certain pathogenic features and for the development and preclinical testing of candidate therapies. They propose to characterize T cells from mice that recognize AQP4 and develop a murine model of NMO that more closely resembles the human disease than those that currently exist. The approach is to identify pathogenic determinants of AQP4 using fragments encompassing the entire sequence of AQP4, as well as the intact AQP4 molecule. Identification of these T cells in humans and mice should also provide insight regarding the development of the humoral (antibody) AQP4-specific response, and may identify new targets for therapeutic intervention.

UCSF, Zamvil Lab Team

• Scott S. Zamvil, M.D., Ph.D., Principal Investigator
  
  
• Patricia A. Nelson, Ph.D., Specialist
  
  
• Collin M. Spencer, Specialist
  
  
• Juan Carlos Patarroyo, Specialist
  
  

Website: http://www.neuroimmunol.org/

 

The Scripps Research Institute

Principal Investigator: Dr. Roberto Baccala
Project Title: Molecular Studies of Neuromyelitis Optica in Mouse Models of Aquaporin-4 Autoimmunity

Neuromyelitis optica (NMO), also known as Devic’s disease, is a chronic inflammatory demyelinating disorder of the central nervous system (CNS) mainly affecting the optic nerves and spinal cord. Because of overlapping clinical characteristics, NMO was frequently misdiagnosed as multiple sclerosis (MS). Accuracy in diagnosis was highly improved by the recent discovery of disease-specific serum autoantibodies (NMO-IgG) with specificity for aquaporin-4 (AQP4), the main water channel in the CNS. Several observations have provided strong indirect evidence that these autoantibodies play a critical role in the physiopathology of NMO. Nevertheless, several important questions remain unresolved, particularly due to the absence of appropriate animal models. The focus of our proposal will be to develop mouse models of AQP4 autoimmunity, drawing from our expertise in autoimmune diseases and mechanisms by which immunological tolerance to self-antigens can be broken. Availability of such models will permit to directly study humoral and cellular contributions to this disease, develop monoclonal antibodies, T cell hybridomas and transgenic mice, and assess novel immunosuppressive therapies for NMO.

The Scripps NMO Team

• Roberto Baccala, PhD, Associate Professor, Department of Immunology and Microbial Science

• Argyrios N. Theofilopoulos, MD, Professor and Chairman, Department of Immunology and Microbial Science

Websites:
http://www.scripps.edu/research/faculty.php?rec_id=4607

http://www.scripps.edu/research/faculty.php?rec_id=1546

 

Johns Hopkins University

Principal Investigator: Dr. Michael Levy
Project Title: Aquaporin 4 variants and astrocyte diversity in the immuno-pathogenesis of NMO

The neuromyelitis optica (NMO) labs at Johns Hopkins University are committed to understand the basic pathogenic mechanisms of NMO. We are using unique features of NMO including the localization of disease to the optic nerves and spinal cord and the presence of the anti-aquaporin-4 (AQP4) antibody, the NMO-IgG, to study the difference between NMO and other inflammatory diseases of the nervous system. We are focusing on the expression of the AQP4 water channels as the primary player in the pathogenesis of disease. Using techniques such as flow cytometry, real time PCR and gene chip analysis, we are beginning to undercover the roles of AQP4 and AQP4-related proteins in NMO.

Johns Hopkins NMO team:

• Michael Levy, MD, PhD, Neuroimmunology Fellow and director of the NMO clinic

• Carlos Pardo, MD, Associate Professor

• Douglas Kerr, MD, PhD, Associate Professor and director of the Transverse Myelitis clinic

• Harleen Saini, MS, research associate