Protective effect of a novel free radical scavenger, OPC-14117, on wobbler mouse motor neuron disease

Abstract

A possible protective effect of a novel free radical scavenger, OPC-14117, on the progressive motor neuron death in wobbler mice was examined. Clinical parameters such as mortality, body weight, motor activity as a rolling number of circular cage, and forelimb muscle power as grasping on a rolling column, an angle of slipping down from slope, and hanging ability on a flat plate were compared every 4 weeks from 4 to 36 weeks of age among mice groups treated with vehicle or daily oral administration of OPC-14117 of 10 or 30 mg/kg body weight. The treatment with OPC-14117 dose dependently improved the clinical parameters such as mortality, motor activity, and forelimb weakness. Pathological analysis showed that a diffuse neurogenic change in the forelimb muscle was improved at 36 weeks of age in the drug treated mice with a marked preservation of motor neurons in the spinal cord. Treatment of the mice with the drug reduced age-dependent increase of lipid peroxides in the spinal cord in vivo, and a supplement of the drug to the homogenate of spinal cord in vitro ameliorated the formations of lipid peroxides generated by an exogenous addition of ascorbate or xanthine/xanthine oxidase. These results suggest that OPC-14117 has a protective effect on the motor neuron death probably as a free radical scavenger, resulting in an improvement of clinical symptoms in wobbler mice.