The research interests of Bharath Wootla, Ph.D., involve the endogenous repair of central nervous system injury through naturally occurring molecules. Dr. Wootla works in close collaboration with Moses Rodriguez, M.D.
Repair of damaged tissue is a prerequisite for the restoration of function. To this end, Dr. Wootla and colleagues in Dr. Rodriguez's laboratory are interested in developing strategies to promote regeneration of the central nervous system after injury.
Multiple sclerosis (MS). Dr. Wootla and colleagues in Dr. Rodriguez's lab pioneered the discovery of naturally occurring human antibodies that trigger remyelination both in vivo and in vitro. These antibodies promote remyelination and functional improvement in three experimental models of MS (viral, autoimmune and toxic). Dr. Wootla's primary interest is to understand whether antibody-mediated promotion of remyelination preserves axons from death in a viral mouse model of human MS.
Dr. Wootla collaborates with Louis (Jim) J. Maher III, Ph.D. on investigations of folded nucleic acid shapes (aptamers) to stimulate remyelination of the central nervous system and regeneration of locomotor function after damage due to virus-induced demyelination. A different project involves studying aptamers in the toxin-induced model of demyelination.
- Amyotrophic lateral sclerosis (ALS). Recombinant natural human antibody IgM12 binds to the surface of neurons and supports neurite extension. Dr. Wootla is investigating the use of rHIgM12 as a therapeutic strategy in murine models of human ALS.
Neuromyelitis optica (NMO). Antibody enzymes (abzymes) are antibody catalysts with hydrolytic properties that exhibit rate accelerations, substrate specificity, and regio- and stereo-selectivity. Such antibodies were previously reported under inflammatory, autoimmune, neoplastic or alloimmune conditions and were shown to play a deleterious role.
Dr. Wootla is investigating the presence of these antibodies in the sera of patients with NMO. This research is carried out in collaboration with Sean J. Pittock, M.D.
Significance to patient care
Dr. Wootla aspires to identify better therapeutic strategies for various neurological diseases.
His current research efforts tap into the therapeutic potential of naturally occurring human IgM antibody molecules. His application model focuses on remyelination and associated repair, but the promise of such therapeutic applications reach well beyond remyelination.
Dr. Wootla and colleagues in Dr. Rodriguez's laboratory combine basic research with translational research and apply the basic understanding to diseases such as MS and ALS. To highlight one example, the recombinant human monoclonal IgM antibody, rHIgM22, which binds specifically to live oligodendrocytes and myelin, recently completed a 16-site phase I clinical trial in 72 patients with MS with complete safety.
- Prix de thèse "Guy Deniélou" (best thesis award), Université de Technologie de Compiègne (France), 2008