Atsena Therapeutics has announced that dosing has begun for the second cohort in LIGHTHOUSE, a phase 1/2 clinical trial evaluating subretinal injection of ATSN-201, a gene therapy intended to treat X-linked retinoschisis (XLRS). ATSN-201 leverages AAV.SPR, the company’s novel spreading capsid, to achieve therapeutic levels of gene expression in photoreceptors of the central retina while avoiding the surgical risks of foveal detachment.
XLRS is a monogenic X-linked disease caused by mutations in the RS1 gene which encodes retinoschisin, a protein secreted primarily by photoreceptors. RS1 is localized to the extracellular surface of rods, cones, and bipolar cells. XLRS is characterized by schisis, or abnormal splitting of retinal layers, which causes impaired visual acuity that is not correctable with glasses and leads to progressive vision loss and ultimately blindness. XLRS primarily affects males and is typically diagnosed in early childhood. Approximately 30,000 males in the United States and European Union have XLRS, for which there are currently no approved treatments.
The LIGHTHOUSE study1 is an open-label, dose-escalation and dose-expansion clinical trial evaluating the safety and tolerability of ATSN-201 in male patients ages 6 and older with a clinical diagnosis of XLRS caused by pathogenic or likely pathogenic mutations in RS1. Enrollment in LIGHTHOUSE is ongoing. ATSN-201 was well tolerated in all 3 patients in the first cohort and no serious adverse events were reported, the company said. The Data and Safety Monitoring Board recommended proceeding with the second cohort, in which patients will receive the next dose level of ATSN-201.
"We are encouraged by the excellent safety observed with the low dose of ATSN-201 in the LIGHTHOUSE study, which represents the first clinical utilization of AAV.SPR,” said Kenji Fujita, MD, chief medical officer of Atsena Therapeutics, in a news release. “Additionally, initial indications of structural and functional improvement observed within and beyond the injection areas suggest successful lateral spread of the vector.”
References
- ATSN-201 gene therapy in RS1-associated X-linked retinoschisis (LIGHTHOUSE). ClinicalTrials.gov identifier: NCT05878860. Updated March 6, 2024. Accessed March 13, 2024. https://www.clinicaltrials.gov/study/NCT05878860
