Seelos Therapeutics Announces Data Demonstrating Statistically Significant Downregulation of mRNA and Reduction of Alpha Synuclein in an In Vitro Gene Therapy Study of SLS-004 Utilizing CRISPR-dCas9 in Dementia with Lewy Bodies
Preliminary Findings of In Vitro Study
The goal of this in vitro study was to extend the existing SNCA-targeted epigenome therapy system (SLS-004) by modifying the viral vector to target specific cholinergic neurons in the cortex that are afflicted in DLB and validate the specificity and efficacy in human-induced pluripotent stem cells (hiPSC) derived neuronal systems.
The parental line SNCA-Tri hiPSC-derived system for the proof-of-concept model was utilized for the current study. hiPSC were differentiated utilizing earlier protocols used in SLS-004. Multiple batches of each differentiated neuronal type were evaluated, and successful differentiation of each batch was established.
The preliminary findings showed that following two weeks of differentiation into cholinergic neurons, there was a statistically significant (p<0.01) 19% downregulation of mRNA and a ~40% reduction of α-synuclein protein compared to the no treatment/repressor groups.
Seelos plans to advance the study of SLS-004 in DLB in additional preclinical studies and disclose further developments of this new CRISPR-based therapeutic technology in the future.
In July 2021, Seelos released positive preclinical in vivo data with SLS-004 in downregulation of overexpressed α-synuclein in a Parkinson's disease model and plans to release additional data in the second half of 2022.
