PRO135

**PRO135** is an investigational antisense oligonucleotide (AO) developed by Prosensa Therapeutics for the treatment of **Myotonic Dystrophy type 1 (DM1)**, a rare genetic disorder caused by CTG triplet repeat expansions in the 3' untranslated region of the **DMPK** gene, leading to toxic RNA transcripts that sequester RNA-binding proteins and disrupt splicing. It employs RNA modulation to target and reduce these expanded repeat toxic transcripts via **RNase H1-mediated degradation**, reversing transcript toxicity as demonstrated in preclinical **in vivo** intramuscular administration models of DM1. Developed in collaboration with Radboud University Nijmegen Medical Centre, PRO135 received Dutch government innovation funding in 2011 but remains at the preclinical stage with no reported clinical trials.[1][2]