PROTECTIVE EFFECT OF A NOVEL FREE-RADICAL SCAVENGER, OPC-14117, ON WOBBLER MOUSE MOTOR-NEURON DISEASE

A possible protective effect of a novel free radical scavenger, OPC-14 117, on the progressive motor neuron death in wobbler mice was examine d. Clinical parameters such as mortality, body weight, motor activity as a rolling number of circular cage, and forelimb muscle power as gra sping on a rolling column, an angle of slipping down from slope, and h anging ability on a flat plate were compared every 4 weeks from 4 to 3 6 weeks of age among mice groups treated with vehicle or daily oral ad ministration 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 ana lysis showed that a diffuse neurogenic change in the forelimb muscle w as 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 mic e with the drug reduced age-dependent increase of lipid peroxides in t he 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, result ing in an improvement of clinical symptoms in wobber mice. (C) 1997 Wi ley-Liss, Inc.