Immunosuppressant FK506 does not exert beneficial effects in symptomatic G93A superoxide dismutase-1 transgenic mice

The immunosuppressant drug FK506 has been shown to exert neuroprotective ef fects in various model systems via inhibition of the protein phosphatase ca lcineurin (CN). The enzyme Cu/ Zn-superoxide dismutase (SOD1), which is mut ated in a familial form of amyotrophic lateral sclerosis (ALS), is an endog enous regulator of CN. Altered function of CN may therefore be involved in the pathogenesis of ALS. We tested FK506 in a transgenic mouse model expres sing mutated SOD1 for potential beneficial effects. This treatment, initiat ed after onset of symptoms, did not cause a reduction in the decline of mot or function nor did it prolong survival. These results argue against a cruc ial role of CN in the process leading to motoneuronal degeneration in SOD1- mutated mice. NeuroReport 12:2663-2665 (C) 2001 Lippincott Williams & Wilki ns.