About the Lab
The Multiple Sclerosis Laboratory of Moses Rodriguez, M.D., at Mayo Clinic focuses on determining the mechanisms of demyelination and remyelination in diseases such as multiple sclerosis (MS) through primary animal models of demyelination.
The Multiple Sclerosis Laboratory is particularly interested in developing strategies to promote remyelination in the central nervous system.
Having observed that immunization of Theiler's virus-infected mice with spinal cord homogenate induces remyelination, Dr. Rodriguez and his research team subsequently showed that transfer of immunoglobulins directed against spinal cord into animals chronically infected with Theiler's virus induces remyelination.
As a result, the Multiple Sclerosis Lab generated a series of mouse monoclonal antibodies that promotes remyelination. These antibodies are directed against surface components on oligodendrocytes. These antibodies proved to be natural autoantibodies with germline DNA sequences.
The lab has generated two human monoclonal antibodies that also bind to the surface of rat and human oligodendrocytes and that also promote remyelination in both the Theiler's virus system and the lysolecithin model system. Recombinant antibody has been generated that shows similar promotion of remyelination as the serum antibodies.
Following extensive toxicology testing, one of the antibodies (rHIgM22) has completed phase I clinical trials. These natural human autoantibodies against oligodendrocytes proved to have no toxicity in 72 patients with fixed neurological deficits in multiple sclerosis. In addition, the antibody was seen in the cerebrospinal fluid of all patients tested, indicating that these large molecules do cross the blood-brain barrier. Phase II clinical trials with rHIgM22 are being planned.
Our lab has now generated a new antibody (rHIgM12) that is directed at neurons and axons rather than at oligodendrocytes and that has shown remarkable efficacy in the progressive forms of demyelination characterized by extensive axonal injury. In addition, this antibody has increased the life span of animals with the genetic SOD1 forms of amyotrophic lateral sclerosis (ALS).
Another focus of the laboratory is developing broad-spectrum antiviral agents.
Researchers in Dr. Rodriguez's lab have discovered that transgenic mice expressing the RNA-dependent RNA polymerase of Theiler's virus are resistant to a wide group of both RNA and DNA viruses. The reason for the resistance is that the mice mount a class I interferon response where more than 100 genes controlling virus defense are up-regulated.
Work is underway to determine ways to use this observation to generate a new line of drugs that could be useful to fight bioterrorism or serious viral epidemics.
About Dr. Rodriguez
Moses Rodriguez, M.D., a specialist in neuroregeneration at Mayo Clinic in Rochester, Minnesota, is a nationally recognized multiple sclerosis expert. At Mayo Clinic, Dr. Rodriguez holds the academic rank of professor of neurology and immunology and holds the Mildred A. and Henry Uihlein II Professorship in Medical Research. He earned his B.A. degree in medical sciences and his M.D. degree from Northwestern University.
After residency in internal medicine and a residency in neurology at Mayo Graduate School of Medicine, Dr. Rodriguez served as a trainee at the National Institutes of Health and completed fellowships in neuropathology at the University of California, San Diego, and at Scripps Research Institute.
Dr. Rodriguez has made significant contributions to both the clinical and basic science aspects of multiple sclerosis research.
Clinically, he has been instrumental in population-based cohort studies of approximately 200 patients with multiple sclerosis in the Olmsted County, Minnesota, population. These resulted in a number of significant discoveries.
His work revealed that the progression of neurological deficits in multiple sclerosis is slower than anticipated. He has also helped to identify a cohort of patients that appears to have a nondisabling type of multiple sclerosis, which has provided important data regarding the clinical management of patients with multiple sclerosis.
Dr. Rodriguez was the first to demonstrate conclusively that plasma exchange is effective in patients with severe, devastating attacks of multiple sclerosis. In a series of studies, he showed that patients with acute onset paraplegia, quadriplegia or respiratory insufficiency remarkably recovered following plasma exchange.
These results were confirmed in a double-blind, placebo-controlled trial performed at Mayo Clinic, which demonstrated that approximately 40 percent of patients have dramatic recovery following this treatment. These results have changed the management of acute devastating attacks of multiple sclerosis.
On the basic science side, Dr. Rodriguez has made three seminal discoveries: the CD8 T cell's role in demyelination/axonal injury; the remyelinating mechanism in human monoclonal antibodies; and the axon-protective role of IL6, all of which have been awarded patents.
In a work published in Nature Medicine, Dr. Rodriguez demonstrated for the first time that CD8 T cells are critical for the destruction of axons. T cells work by recognizing class I MHC molecules. He also has identified that perforin is the critical molecule in axonal injury and death.
In the field of remyelination, Dr. Rodriguez has identified a series of human monoclonal antibodies that bind to the surface of oligodendrocytes. These antibodies trigger the remyelination program both in vivo and in vitro.
Dr. Rodriguez has demonstrated that interleukin-6 is critical in protecting neurons and axons from death in a demyelinating lesion.
Dr. Rodriguez's work has resulted in patent awards to him and Mayo Clinic, signaling that these discoveries may soon be used in patient treatment.
Read more about Dr. Rodriguez's research activities.