A new gene therapy for X-linked retinoschisis (XLRS) has received Orphan Drug Designation from the U.S. Food and Drug Administration (FDA). This rare genetic disorder affects the retina, causing vision loss primarily in males. The designation marks a crucial step forward in addressing the unmet medical needs of individuals living with this challenging condition.
ATSN-201 is a novel gene therapy being developed by Atsena Therapeutics. This treatment aims to tackle the root cause of XLRS by delivering a functional copy of the RS1 gene to affected cells in the retina. The FDA’s decision has significant implications for the development and potential availability of this therapy, offering hope to patients and their families who have long awaited effective treatment options for this debilitating eye disorder.
Understanding X-Linked Retinoschisis (XLRS)
XLRS is a rare genetic disorder affecting primarily males, characterized by reduced visual acuity due to juvenile macular degeneration [1]. The condition is caused by mutations in the RS1 gene, located on the X chromosome, which provides instructions for producing retinoschisin, a protein essential for retinal development and maintenance [2] [3].
XLRS manifests in the first decade of life, with symptoms including poor vision and reading difficulties [4]. The prevalence of XLRS is estimated to range between 1/5,000-1/25,000 males worldwide [5]. The disorder results in tiny splits (schisis) or tears in the retina, often forming a characteristic ‘spoke-wheel’ pattern in the macula visible during eye examinations [6].
Clinically, XLRS is a symmetrical bilateral macular disorder. In severe cases, patients may experience full-thickness retinal detachment, vitreous hemorrhage, and neovascular glaucoma, leading to significant vision loss [7]. The disease typically progresses slowly until adolescence, stabilizes during young adulthood, and may decline again in the fourth or fifth decade of life .
ATSN-201
ATSN-201 utilizes AAV.SPR, a novel spreading capsid, to achieve therapeutic levels of gene expression in retinal photoreceptors while avoiding foveal detachment risks [1].
The LIGHTHOUSE study, a Phase 1/2 clinical trial, is evaluating ATSN-201’s safety and efficacy in male patients aged 6 and older with XLRS [3]. Preliminary data from the first cohort has shown promising results, with two out of three patients experiencing extensive schisis resolution beginning at 8 weeks post-treatment [4]. Importantly, the therapy demonstrated lateral spread beyond the injection sites, consistent with the expected behavior of the AAV.SPR capsid [5].
To learn more about rare eye diseases, visit https://checkrare.com/diseases/ophthalmology-eye-diseases/
References
[1] – https://www.biospace.com/agtc-announces-u-s-fda-orphan-drug-designation-for-gene-therapy-to-treat-x-linked-retinitis-pigmentosa
[2] – http://www.techtransfer.nih.gov/tech/tab-4162
[3] – https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=238907
[4] – https://www.healio.com/news/ophthalmology/20240815/gene-therapy-for-xlinked-retinoschisis-receives-rare-pediatric-disease-designation
[5] – https://www.ohsu.edu/casey-eye-institute/clinical-trial-marks-new-chapter-gene-therapy
[6] – https://www.fightingblindness.org/news/atsena-s-xlrs-gene-therapy-shows-efficacy-in-phase-1-2-clinical-trial-880
[7] – https://medlineplus.gov/genetics/condition/x-linked-juvenile-retinoschisis/
