Atsena Therapeutics Advances Gene Therapy For XLRS

By Erin Harris, Editor-In-Chief, Cell & Gene
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While the CGT sector has made significant strides in oncology, its transformative potential extends well beyond cancer. A growing number of companies are advancing CGT approaches for rare and inherited diseases, including those affecting vision. Atsena Therapeutics, a clinical-stage gene therapy company, exemplifies this shift, focusing its efforts on developing gene therapies for non-oncology indications such as X-linked retinoschisis (XLRS), a debilitating retinal disorder with no approved treatments.

Back in March, I had the pleasure of talking to Atsena’s CMO, Dr. Kenji Fujita on episode 99 of Cell & Gene: The Podcast about the company’s targeted approach, the rationale behind its delivery method, and what makes its pipeline stand out. Indeed, during our discussion, Dr. Fujita explained that XLRS is a monogenic retinal disorder caused by mutations in the RS1 gene, which encodes the retinoschisin protein. This condition affects approximately 30,000 males worldwide and often leads to vision loss beginning in childhood. With no approved treatments currently available, Atsena’s investigational gene therapy offers a promising avenue for patients and clinicians alike.

Understanding the Therapeutic Strategy for XLRS

XLRS primarily affects the retina, leading to structural splitting of the retinal layers —particularly in the macula — resulting in decreased visual acuity. The underlying cause is a deficiency or malfunction of the retinoschisin protein, which plays a critical role in retinal cellular adhesion and fluid regulation. Atsena’s gene therapy is designed to deliver a functional RS1 gene using an AAV vector, enabling the retina to produce retinoschisin and restore its structural and functional integrity.

“This disease is driven by a single genetic defect, making it well-suited for gene therapy,” said Dr. Fujita. “We believe our approach has the potential to significantly improve vision for patients who currently have no treatment options.”

Precision Delivery via Subretinal Injection

While many ocular gene therapies utilize intravitreal injection due to its less invasive nature, Atsena has opted for subretinal delivery. The rationale is both scientific and strategic. “Intravitreal delivery has been unsuccessful in XLRS,” Dr. Fujita explained. “The RS1 gene must be delivered to photoreceptors and bipolar cells, which are not efficiently transduced with standard AAVs via the intravitreal route.”

By delivering the gene therapy directly under the retina, Atsena ensures more precise targeting of the affected cells. This method also allows the use of lower vector doses, which may reduce systemic and local adverse events.

Early Clinical Insights and the Road Ahead

The company’s lead candidate, ATSN-201, is currently being evaluated in the Lighthouse Study, a Phase 1/2 clinical trial enrolling patients aged 6 to 64. Early clinical data, including safety assessments and exploratory efficacy signals, are expected in the first half of this year. Importantly, ATSN-201 utilizes AAV.SPR, a novel vector developed by Atsena’s scientific co-founder Dr. Shannon Boye, specifically optimized for safe and effective subretinal delivery. “Safety is our top priority,” noted Dr. Fujita. “We’re carefully assessing outcomes such as changes in best-corrected visual acuity, retinal sensitivity, and imaging markers such as schisis cavity resolution.”

A Versatile Platform for Retinal Diseases

Beyond XLRS, Atsena is applying its proprietary AAV.SPR vector to other inherited retinal diseases. The company’s preclinical pipeline includes programs targeting retinal disorders where precise subretinal delivery is critical, including Leber congenital amaurosis (LCA1) and other forms of macular degeneration. “What differentiates us is our ability to match the right vector and delivery method to the specific disease biology,” said Dr. Fujita. “We’re not taking a one-size-fits-all approach; we’re engineering precision therapies tailored to each condition.”

The Broader Impact of XLRS Therapy

For the XLRS community, a successful gene therapy would be transformative. Many patients experience progressive vision loss that interferes with education, employment, and daily life. By intervening early, Atsena aims to halt or even reverse this decline. “We’re inspired every day by the patients and families we serve,” said Dr. Fujita. “Our mission is to bring life-changing treatments to those affected by inherited retinal diseases, and XLRS is just the beginning.”