ANTI-GM(1) GD(1B) M-PROTEINS DAMAGE HUMAN SPINAL-CORD NEURONS COCULTURED WITH MUSCLE/

IgM M-proteins in some motor neuron disease (MND) patients bind immuno logically to shared determinants on gangliosides GM1 and GD1b. Since p atients with these M-proteins have improved with immunotherapy the ant ibodies may be important in the pathogenesis of MND. To study how the M-proteins might damage motor neurons, we established co-cultures of h uman neurons from spinal cord explants and human myotubes. Antibodies from patient but not control serum bound to the cultured neurons. Neur ons in co-cultures degenerated after incubation with patient but not c ontrol serum. These results demonstrate that anti-GM1 antibodies can b ind to and destroy spinal cord neurons that are cultured with muscle. Nerve-muscle co-cultures can serve as a system to examine effects of a nti-GM1/GD1b M-proteins on motor neurons.