)| PMID |
16781706 ( ) |
|---|---|
| Title | AM1241, a cannabinoid CB2 receptor selective compound, delays disease progression in a mouse model of amyotrophic lateral sclerosis. |
| Abstract | 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. Research Institute, 475 Brannan St Suite 220, San Francisco, CA 94107, USA. |
NOTE: Color highlight is limited to the abstract and SciMiner text-mining mode. If you see much more identified targets below from "Targets by SciMiner Summary" and "Targets by SciMiner Full list", they may have been identified from the full text.
Targets by SciMiner Summary
| HUGO ID | Symbol | Target Name | #Occur | ActualStr |
|---|---|---|---|---|
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | 15 | SOD1 | hSOD1 | |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | 2 | amyloid | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 2.7 | after onset of signs in an ALS mouse model (hSOD1 hSOD1 G93A transgenic mice |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 2.7 | progression and improves survival in the ALS mouse model ( hSOD1 G93A transgenic mice even when administered after the onset of |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | amyloid | 1.0 | al. 2003 and cannabinoid CB 2 receptor activation blocks _amp_#x3b2 -amyloid induced microglial activation ( Ramirez et al. 2005 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.9 | Mutations in Cu/Zn Cu Zn superoxide dismutase (SOD1) SOD1 are the primary cause of up to 20% of familial |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.9 | Transgenic mice expressing human SOD1 mutations have been generated |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 2.7 | These hSOD1 mutant transgenic mice exhibit pathologic and cytological neuromuscular degeneration similar |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 2.7 | The hSOD1 G93A mice are used for preclinical testing of compounds for |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 2.7 | Here we report that AM1241 slows disease progression in hSOD1 G93A mice when administered after onset of disease signs |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.9 | Male transgenic mice expressing the human SOD1 G93A (B6SJL-TgN[SOD1-G93A]1Gur) B6SJL-TgN SOD1-G93A 1Gur ( hSOD1 G93A mice were |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 2.7 | expressing the human SOD1 G93A (B6SJL-TgN[SOD1-G93A]1Gur) B6SJL-TgN SOD1-G93A 1Gur ( hSOD1 G93A mice were bred with background matched B6SJL wild type |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.9 | genotyped using primers specific to exon 4 of the human SOD1 gene within the transgenic construct and segregated and used for |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 2.7 | hSOD1 G93A mice were injected intraperitoneally with vehicle (18:1:1 18 1 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 2.7 | here indicate that AM1241 delays progression of disease in male hSOD1 G93A mice when administered after onset of signs |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 2.7 | phytoestrogen delayed disease onset and mortality when given to male hSOD1 G93A mice reversing the sexual dimorphism normally seen in this |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 2.7 | found to slow disease progression without ultimately affecting survival of hSOD1 G93A mice including cannabinol another cannabinoid compound ( Weydt et |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 2.7 | Microglia from hSOD1 G93A mice possess increased cytotoxic potential ( Weydt et al. |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | amyloid | 1.0 | Cannabinoid CB 2 receptor activation blocks _amp_#x3b2 -amyloid induced microglial activation ( Ramirez et al. 2005 |