| First Author | Koval ED | Year | 2013 |
| Journal | Hum Mol Genet | Volume | 22 |
| Issue | 20 | Pages | 4127-35 |
| PubMed ID | 23740943 | Mgi Jnum | J:201087 |
| Mgi Id | MGI:5510917 | Doi | 10.1093/hmg/ddt261 |
| Citation | Koval ED, et al. (2013) Method for widespread microRNA-155 inhibition prolongs survival in ALS-model mice. Hum Mol Genet 22(20):4127-35 |
| abstractText | microRNAs (miRNAs) are dysregulated in a variety of disease states, suggesting that this newly discovered class of gene expression repressors may be viable therapeutic targets. A microarray of miRNA changes in ALS-model superoxide dismutase 1 (SOD1)(G93A) rodents identified 12 miRNAs as significantly changed. Six miRNAs tested in human ALS tissues were confirmed increased. Specifically, miR-155 was increased 5-fold in mice and 2-fold in human spinal cords. To test miRNA inhibition in the central nervous system (CNS) as a potential novel therapeutic, we developed oligonucleotide-based miRNA inhibitors (anti-miRs) that could inhibit miRNAs throughout the CNS and in the periphery. Anti-miR-155 caused global derepression of targets in peritoneal macrophages and, following intraventricular delivery, demonstrated widespread functional distribution in the brain and spinal cord. After treating SOD1(G93A) mice with anti-miR-155, we significantly extended survival by 10 days and disease duration by 15 days (38%) while a scrambled control anti-miR did not significantly improve survival or disease duration. Therefore, antisense oligonucleotides may be used to successfully inhibit miRNAs throughout the brain and spinal cord, and miR-155 is a promising new therapeutic target for human ALS. |
