ABSENCE OF MHC CLASS-II MOLECULES REDUCES CNS DEMYELINATION, MICROGLIAL MACROPHAGE INFILTRATION, AND TWITCHING IN MURINE GLOBOID-CELL LEUKODYSTROPHY/

Globoid cell leukodystrophy (GLD) is a severe genetic demyelinating di sorder with an increased number of la (immune response antigen) positi ve brain microglial macrophages. To assess the role of aberrant la exp ression in the central nervous system (CNS), twitcher mice, which repr esent the murine model for GLD, were mated with la(-) transgenic mice. Compared with the la(+) controls, la(-) twitcher mice showed a profou nd reduction in the severity of demyelinating lesions correlated with significantly fewer microglia/macrophages. Most importantly, la(-) twi tcher mice showed significantly reduced twitching compared with la(+) twitcher mice. In contrast with experimental allergic encephalomyeliti s (EAE), there was no significant amount of inflammatory T cell infilt rates, implying that T eels may not play a predominant role in this di sease. These findings may have broad therapeutic implications for Alzh eimer's disease, Parkinson's disease, and Huntington's disease, which display enhanced la expression in the CNS without obvious T cell infil trates.