| First Author | Bersani M | Year | 2022 |
| Journal | Mol Ther | Volume | 30 |
| Issue | 3 | Pages | 1288-1299 |
| PubMed ID | 34808387 | Mgi Jnum | J:355201 |
| Mgi Id | MGI:7737849 | Doi | 10.1016/j.ymthe.2021.11.012 |
| Citation | Bersani M, et al. (2022) Cell-penetrating peptide-conjugated Morpholino rescues SMA in a symptomatic preclinical model. Mol Ther 30(3):1288-1299 |
| abstractText | Spinal muscular atrophy (SMA) is a motor neuron disease and the leading genetic cause of infant mortality. Recently approved SMA therapies have transformed a deadly disease into a survivable one, but these compounds show a wide spectrum of clinical response and effective rescue only in the early stages of the disease. Therefore, safe, symptomatic-suitable, non-invasive treatments with high clinical impact across different phenotypes are urgently needed. We conjugated antisense oligonucleotides with Morpholino (MO) chemistry, which increase SMN protein levels, to cell-penetrating peptides (CPPs) for better cellular distribution. Systemically administered MOs linked to r6 and (RXRRBR)(2)XB peptides crossed the blood-brain barrier and increased SMN protein levels remarkably, causing striking improvement of survival, neuromuscular function, and neuropathology, even in symptomatic SMA animals. Our study demonstrates that MO-CPP conjugates can significantly expand the therapeutic window through minimally invasive systemic administration, opening the path for clinical applications of this strategy. |
