AM1241, a cannabinoid CB2 receptor selective compound, delays disease progression in a mouse model of amyotrophic lateral sclerosis

Effective treatment for amyotropbic 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. AM 1241 is a cannabinoid CB, 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 (hSODI(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, AM 1241 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 CB, receptor-selective compounds maybe the basis for developing new drugs for the treatment of ALS and other chronic neurodegenerative diseases. (c) 2006 Elsevier B.V. All rights reserved.