Anti-GM1/GD1b M-proteins damage human spinal cord neurons co-cultured with muscle

IgM M-proteins in some motor neuron disease (MND) patients bind immunologically to shared determinants on gangliosides GM₁ and GD_1b. Since patients with these M-proteins have improved with immunotherapy the antibodies may be important in the pathogenesis of MND. To study how the M-proteins might damage motor neurons, we established co-cultures of human neurons from spinal cord explants and human myotubes. Antibodies from patient but not control serum bound to the cultured neurons. Neurons in co-cultures degenerated after incubation with patient but not control serum. These results demonstrate that anti-GM₁ antibodies can bind to and destroy spinal cord neurons that are cultured with muscle. Nerve-muscle co-cultures can serve as a system to examine effects of anti-GM₁/GD_1b M-proteins on motor neurons.