Axonal protection achieved in a model of multiple sclerosis using lamotrigine

Axonal degeneration is a major cause of permanent disability in multiple sclerosis (MS). Recent observations from our and other laboratories suggest that sodium accumulation within compromised axons is a key, early step in the degenerative process, and hence that limiting axonal sodium influx may represent a mechanism for axonal protection in MS. Here we assess whether lamotrigine, a sodium channel-blocking agent, is effective in preventing axonal degeneration in an animal model of MS, namely chronic-relapsing experimental autoimmune encephalomyelitis (CR-EAE). When administered from 7 days post-inoculation, lamotrigine provided a small but significant reduction in the neurological deficit present at the termination of the experiments (averaged over three independent experiments; vehicle: 3.5 ± 2.7; lamotrigine: 2.6 ± 2.0, P < 0.05) and preserved more functional axons in the spinal cord (measured as mean compound action potential area; vehicle: 31.7 μV.ms ± 23.0; lamotrigine: 42.9 ± 27.4, P < 0.05). Histological examination of the thoracic spinal cord (n = 71) revealed that lamotrigine treatment also provided significant protection against axonal degeneration (percentage degeneration in dorsal column; vehicle: 33.5 % ± 38.5; lamotrigine: 10.4 % ± 12.5, P < 0.01). The findings suggest that lamotrigine may provide a novel avenue for axonal protection in MS.