Methionine-free brain-derived neurotrophic factor in wobbler mouse motor neuron disease: dose-related effects and comparison with the methionyl form

Abstract

We compared the clinical and pharmacodynamic effects of N-terminal methionine brain-derived neurotrophic factor (met-BDNF) and endogenous met-free BDNF in wobbler mouse motor neuron disease (MND). Met- or met-free BDNF at 5 or 20 mg/kg was subcutaneously injected daily, six times/week for 4 weeks. At 20 mg/kg, grip strength ( P<0.05, met-free BDNF; P<0.01, met-BDNF) and running speed ( P<0.01 for both groups) improved compared to vehicle. At 5 mg/kg, the beneficial effect was more modest. Plasma BDNF levels after the final injection were dose-dependent and did not differ between BDNF groups. Endogenous met-free BDNF exerts effects similar to met-BDNF in wobbler MND.