Potential Parkinson disease and ALS drug

Nature Genetics 44,1178 (2012)

Pamela Feliciano

“Potential Parkinson disease and ALS drug”

The aminopropyl carbazole compound P7C3 has previously been reported to have proneurogenic, neuroprotective properties in adult mice. Now, in two papers, Andrew Pieper and colleagues report the neuroprotective effects of a variant of P7C3 (P7C3A20) in mouse models of amyotrophic lateral sclerosis (ALS) and Parkinson disease. Tesla et al. (Proc. Natl. Acad. Sci. USA, published online 1 October 2012; doi:10.1073/pnas.1213960109) show that administration of P7C3A20 at the time of disease onset in G93A-SOD1 mutant mice (a mouse model of ALS) provides significant protection from spinal motor neuron cell death. After about 2 weeks of treatment, P7C3A20-treated mice displayed improved rotarod performance. Significant improvements were also observed in walking gait. In another paper, the authors used toxin-induced models of Parkinson disease, including a model in which mice are exposed to the potent, selective toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) that kills dopaminergic neurons. De Jesús-Cortés et al. report that P7C3A20 confers protection from MPTP-induced neuronal cell death in mice (Proc. Natl. Acad. Sci. USA, published online 1 October 2012; doi:10.1073/pnas.1213956109). The authors also found that P7C3A20 blocks 1-methyl-4-phenylpyridinium (MPP⁺)-induced dopaminergic neuronal death in Caenorhabditis elegans. MPP⁺-exposed worms treated with P7C3A20 also showed improvements in locomotion. The two studies suggest that further work on P7C3A20 or another P7C3 variant may lead to effective treatments for neurodegenerative diseases.