Colivelin prolongs survival of an ALS model mouse.
Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease for which there is no sufficiently effective therapy. We have reported in our earlier study that intracerebroventricular (i.c.v.) injection of activity-dependent neurotrophic factor (ADNF) improves motor performance of G93A-SOD1 transgenic mice without significant prolongation in survival. Here, we found that i.c.v. injection of a synthetic hybrid peptide named Colivelin composed of ADNF and AGA-(C8R)HNG17, a potent derivative of Humanin that is a bioactive peptide with anti-Alzheimer's disease activity, dose-dependently improved motor performance and prolonged survival of ALS mice. Histological analysis, performed at the age of 120 days, demonstrated increased motoneuronal survival in spinal cords of Colivelin-treated mice as compared with saline- or ADNF-treated mice, indicating that Colivelin is a promising neurotrophic peptide for treatment of ALS.
Department of Pharmacology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Tomohiro
T
Chiba
Marina
M
Yamada
Jumpei
J
Sasabe
Kenzo
K
Terashita
Sadakazu
S
Aiso
Masaaki
M
Matsuoka
Ikuo
I
Nishimoto
D017668:Age of Onset; D000690:Amyotrophic Lateral Sclerosis / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D047908:Intracellular Signaling Peptides and Proteins / Q000627:therapeutic use*; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000187:drug effects; D009046:Motor Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D013116:Spinal Cord / Q000473:pathology; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1; D016019:Survival Analysis
C508523:Colivelin; D047908:Intracellular Signaling Peptides and Proteins; D018696:Neuroprotective Agents; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1