AM1241, a cannabinoid CB2 receptor selective compound, delays disease progression in a mouse model of amyotrophic lateral sclerosis.
Effective treatment for amyotrophic lateral sclerosis (ALS) remains elusive. Motor neuron degeneration is the primary pathology in ALS; however non-neuronal cells contribute to the disease process. In particular, inflammatory processes have been shown to play an important role. AM1241 is a cannabinoid CB2 receptor selective agonist that has been shown to be effective in models of inflammation and hyperalgesia. Here we report that treatment with AM1241 was effective at slowing signs of disease progression when administered after onset of signs in an ALS mouse model (hSOD1(G93A) transgenic mice). Administration at the onset of tremors delayed motor impairment in treated mice when compared to vehicle controls. Three conditions of ALS, the loss of motor function, paralysis scoring and weight loss, were analyzed using a mathematical model. Loss of motor function (as assessed by performance on a rotarod) was delayed by 12.5 days in male mice by AM1241. In female mice, AM1241 extended rotarod performance by 3 days, although this was not statistically significant. In male mice, AM1241 also extended by 5 days the time to reach the 50% point on a visually-assessed performance scale. AM1241 did not affect weight loss or survival (129.8+/-1.7 days, vehicle; 129.1+/-7.0 days, AM1241, n=16). As AM1241 was well tolerated by the animals, cannabinoid CB2 receptor-selective compounds may be the basis for developing new drugs for the treatment of ALS and other chronic neurodegenerative diseases.
Kim
Kathline
K
Forbes Norris MDA/ALS Research Center, California Pacific Medical Center Research Institute, 475 Brannan St Suite 220, San Francisco, CA 94107, USA.
Moore
Dan H
DH
Makriyannis
Alexandros
A
Abood
Mary E
ME
D019943:Amino Acid Substitution / Q000235:genetics; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000503:physiopathology / Q000517:prevention & control*; D000818:Animals; D002186:Cannabinoids / Q000737:chemistry / Q000494:pharmacology; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008958:Models, Molecular; D009043:Motor Activity / Q000187:drug effects; D009154:Mutation / Q000235:genetics; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists*; D012737:Sex Factors; D013482:Superoxide Dismutase / Q000235:genetics
C439263:AM 1241; D002186:Cannabinoids; D043885:Receptor, Cannabinoid, CB2; C109415:SOD1 G93A protein; D013482:Superoxide Dismutase