Tuesday, August 29, 2023
Atsena Therapeutics has achieved a significant milestone in its pursuit of treating X-linked retinoschisis (XLRS), a genetic eye disorder. The company has announced the dosing of the first patient in its Phase I/II clinical trial known as the LIGHTHOUSE study. This trial focuses on evaluating the effectiveness of ATSN-201, an experimental treatment that involves a subretinal injection, for XLRS.
The uniqueness of ATSN-201 lies in its utilization of AAV.SPR, a novel spreading capsid developed by Atsena. This innovative approach allows for targeted gene expression in the photoreceptors of the central retina, all while sidestepping the potential surgical complications related to foveal detachment.
Dr. Kenji Fujita, Chief Medical Officer of Atsena Therapeutics, expressed optimism about this development, emphasizing the transformative potential of AAV.SPR not only for XLRS but also for addressing other inherited retinal disorders. The key advantage of AAV.SPR is its lateral spreading capability from the subretinal injection site. This unique property ensures the safe and effective delivery of the RS1 gene to the photoreceptors in the central retina, addressing a significant challenge in gene therapy.
The LIGHTHOUSE study, designed as a Phase I/II clinical trial, adopts an open-label approach that includes dose escalation and expansion. The primary goal is to assess the safety and tolerability of ATSN-201 in male patients aged 6 to 64 who have been clinically diagnosed with XLRS due to specific genetic mutations in the RS1 gene.
Dr. Mark Pennesi, a prominent figure in Ophthalmology and Chief of the Paul H. Casey Ophthalmic Genetics Division Molecular and Medical Genetics at Oregon Health & Science University (OHSU), highlighted the significance of this milestone for individuals affected by inherited retinal diseases. He underscored the potential breakthrough that subretinal treatment with spreading AAV vectors could represent, particularly considering the current lack of effective XLRS therapies.
XLRS is a monogenic X-linked disease resulting from mutations in the RS1 gene, responsible for producing the retinoschisin protein. This condition leads to the abnormal splitting of retina layers, causing progressive vision loss that is not correctable with conventional methods. XLRS predominantly affects males and is usually diagnosed in early childhood. Presently, approved treatments for this condition are lacking, leaving around 30,000 affected males in the U.S. and EU without effective options.
The introduction of AAV.SPR, a novel spreading capsid by Atsena, holds the promise of overcoming delivery challenges associated with gene therapy. Unlike traditional methods, AAV.SPR's lateral spread beyond the subretinal injection area allows for efficient transduction of the central retina. This is particularly relevant as XLRS patient retinas often exhibit schisis cavities in this region. A preclinical study involving non-human primates showcased AAV.SPR's ability to achieve transgene expression beyond the initial injection site, a contrast to established vector AAV5. Additionally, AAV.SPR demonstrates effective transduction of foveal cones at clinically relevant doses without necessitating surgical detachment or causing inflammation.