Promoting Remyelination

Basic science projects

Over the last twenty years, the Rodriguez laboratory has identified a series of monoclonal antibodies that enhance remyelination in animal models of MS (supported by NIH R01 NS24180). These include a viral model (Theiler's virus-induced demyelination), a toxic model (lysolecithin-induced demyelination), and an autoimmune model (experimental autoimmune encephalomyelitis induced by MOG protein).

The goal of these studies is to determine how antibodies promote new synthesis of myelin and CNS repair. Antibodies identified to date bind to the surface of oligodendrocytes and to lipids or gangliosides in membranous lipid rafts to trigger a signaling cascade instructing the oligodendrocytes to myelinate. (Under the MS Center grant CA1011)

The short-term goal is to define the signaling pathways that induce myelination and remyelination. This information is essential for designing small molecules with potential to stimulate myelin repair by acting on this signaling pathway. Development of assays to monitor beneficial manipulation of the signaling pathway, in collaboration with pharmaceutical companies, will allow rapid screening of >100,000 compounds for their potential to enhance myelin repair. The project is funded by grants from National Institutes of Health (R01 NS24180) and the National Multiple Sclerosis Society (RG 3172).

Clinical projects

The Rodriguez laboratory (in collaboration with the Pease laboratory) has generated several human monoclonal antibodies that induce CNS repair. The antibody in most advanced development, designated recombinant IgM 22, has been fully characterized at the molecular level and has been genetically engineered for mass production in a GMP facility at the University of Minnesota. The GMP-produced antibody induces remarkable remyelination without toxic side effects animals with experimentally induced demyelination (work in collaboration with Dr. Ron Marler, Scottsdale, AZ). A planned Phase I/Phase II clinical trial, awaiting approval from the FDA, will evaluate CNS myelin repair in patients with moderate-to-severe neurological deficits from MS. Dr. Warrington, who originally identified IgM22, helped Dr. Rodriguez prepare the IND application for the FDA. This project is funded by a grant from the Hilton Foundation. Dr. Basford's Rehabilitation Training Grant (NIH HD07447) has supported the salaries of postdoctoral fellows in this field of research.