NEW YORK – Atsena Therapeutics on Monday said it has treated the first patient with X-linked retinoschisis (XLRS) with its investigational gene therapy ATSN-201 in a Phase I/II trial.
In the LIGHTHOUSE trial, the Durham, North Carolina-based company hopes to establish a dose for ATSN-201 for later-stage trials and test the gene therapy's safety and tolerability in male patients between ages 6 and 64 with XLRS due to a pathogenic or likely pathogenic RS1 genetic mutation.
XLRS is an inherited disease that causes retinal degeneration and vision loss in males during early childhood. The disease is most commonly due to mutations in the RS1 gene, which is located on the X chromosome and encodes a protein secreted by photoreceptors called retinoschisin.
ATSN-201 uses AAV.SPR, a capsid that Atsena has designed to deliver normal versions of the RS1 gene to photoreceptors beyond the subretinal injection site and into the central retina. With this laterally spreading capsid, Atsena stated that it hopes to induce "therapeutic levels of gene expression in photoreceptors of the central retina while avoiding the surgical risks of foveal detachment."
Around 30,000 males in the US and Europe have XLRS, for which there aren't any approved therapies. As such, the start of the LIGHTHOUSE trial is meaningful to the inherited retinal disease community, noted Mark Pennesi, chief of the ophthalmic genetics division within the medical school at the Oregon Health & Science University, one of the sites where the study is taking place. "While attempts to deliver gene therapy through intravitreal routes faced challenges, subretinal treatment utilizing spreading AAV vectors has the potential to be the breakthrough we need to achieve efficacy."
Atsena is also studying a gene therapy, ATSN-101, for Leber congenital amaurosis, a rare eye disorder caused by GUCY2D genetic mutations. In April, the company said it was hoping to start a pivotal trial for ATSN-101 based on promising Phase I/II data.