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

• Published in: Neuroreport Vol. 12; no. 12; pp. 2663 - 2665
• Main Authors: Anneser, Johanna M. H, Gmerek, Andreas, Gerkrath, Jasmin, Borasio, Gian Domenico, Heumann, Rolf
• Format: Journal Article
• Language: English
• Published: England Lippincott Williams & Wilkins, Inc 28-08-2001
• Subjects: Amino Acid Substitution; Amyotrophic Lateral Sclerosis - drug therapy; Amyotrophic Lateral Sclerosis - genetics; Animals; Behavior, Animal - drug effects; Calcineurin Inhibitors; Disease Models, Animal; Disease Progression; Dose-Response Relationship, Drug; Humans; Immunosuppressive Agents - administration & dosage; Injections, Intraperitoneal; Mice; Mice, Transgenic; Motor Activity - drug effects; Mutation; Superoxide Dismutase - genetics; Superoxide Dismutase-1; Survival Rate; Tacrolimus - administration & dosage; Treatment Failure
• ISSN: 0959-4965; 1473-558X
• DOI: 10.1097/00001756-200108280-00015

The immunosuppressant drug FK506 has been shown to exert neuroprotective effects in various model systems via inhibition of the protein phosphatase calcineurin (CN). The enzyme Cu/Zn-superoxide dismutase (SOD1), which is mutated in a familial form of amyotrophic lateral sclerosis (ALS), is an endogenous regulator of CN. Altered function of CN may therefore be involved in the pathogenesis of ALS. We tested FK506 in a transgenic mouse model expressing mutated SOD1 for potential beneficial effects. This treatment, initiated after onset of symptoms, did not cause a reduction in the decline of motor function nor did it prolong survival. These results argue against a crucial role of CN in the process leading to motoneuronal degeneration in SOD1-mutated mice.