Targeting long non-coding RNAs in neurogenetic disorders
Dr Constantin D'YDEWALLE
Janssen Pharmaceutica NV, Beerse, Belgique
lundi 19 février 2018 - 11h00
- Auditorium, IGBMC
Invité(e) par Génomique fonctionnelle et cancer, Irwin DAVIDSON
The neuromuscular disorder spinal muscular atrophy (SMA) is the most common inherited killer of infants and is caused by insufficient expression of survival motor neuron (SMN) protein. SMA therapeutics development efforts have focused on identifying strategies to increase SMN expression. However, all these approaches have failed due to lack of potency or specificity. Long non-coding RNAs (lncRNA) have recently emerged out of the dark matter of the genome and they appear to play crucial roles in the regulation of expression of protein-coding genes. We identified a lncRNA associated with SMN, SMN-AS1, which is enriched in neurons and transcriptionally repressses SMN expression. Targeted knockdown of SMN-AS1 with antisense oligonucleotides increases SMN expression and improved survival of severe SMA mice. My study is the first proof of concept that targeting a lncRNA to transcriptionally activate SMN can be used as a therapeutic approach for SMA and demonstrates the promise of antisense oligonucleotides targeting lncRNAs as treatment for neurogenetic disorders.