QRL-204

QRL-204 is a splice-switching antisense oligonucleotide (ASO) developed to restore UNC13A function in amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and potentially other neurodegenerative diseases. It was generated using QurAlis’ FlexASO™ platform, which aims to produce ASOs with improved potency and therapeutic index. QRL-204 specifically targets the mis-splicing of the UNC13A gene, an essential regulator of neurotransmitter release at synapses. Mis-splicing of UNC13A is a critical RNA alteration found in up to 63% of ALS patients and about one-third of FTD cases. The drug works by binding selectively to specific mRNA molecules, correcting abnormal processing caused by TDP-43 protein dysfunction or genetic mutations, thereby restoring normal UNC13A protein production and synaptic function. Preclinical data show that QRL-204 increases UNC13A levels, normalizes its localization at synapses, and restores synaptic activity[1][4][7][10].

Other names

UNC13A splice-switching antisense oligonucleotideUNC-13A splice-switching antisense oligonucleotideUNC 13A splice-switching antisense oligonucleotideUNC13A ASOUNC-13A ASOUNC 13A ASO