Atsena Gene Therapy Candidates ATSN-101 and ATSN-201 Receive EMA Orphan Designation

Retinal gene therapy developments reached a notable regulatory milestone in July when Atsena Therapeutics secured orphan drug designation from the European Medicines Agency for two distinct therapeutic candidates, according to a corporate press release. The regulatory action covers ATSN-101 for the treatment of Leber congenital amaurosis and ATSN-201 for X-linked retinoschisis.

The two candidate therapies address rare inherited retinal diseases that currently lack approved medical treatments. Receiving orphan designation from the EMA for both ATSN-101 and ATSN-201 underscores that these programs address significant unmet needs for patients who currently have no treatment options, Atsena CEO Patrick Ritschel said in the release. The announcements were highlighted during presentations at the Association for Research in Vision and Ophthalmology meeting in Denver, where researchers outlined the ongoing clinical trajectory of both programs.

Evaluating Alternative Surgical Delivery Methods for Retinal Gene Therapies

While viral vector gene therapies continue to advance through clinical pipelines, researchers are also working to refine the surgical procedures used to administer them. A study published in the September 2025 issue of Science Advances by Mayo Clinic investigators explores a novel approach to retinal gene therapy using high-concentration fibrin hydrogels encapsulating adeno-associated virus 2-green fluorescent protein (AAV2-GFP), according to Mayo Clinic.

The current standard of care for retinal gene therapy involves subretinal injection, a surgical technique where treatment is injected underneath the retina. While this method has successfully restored functional vision in patients receiving therapies such as Luxturna—which was approved by the Food and Drug Administration in 2017 for RPE65-related inherited retinal dystrophy—it carries inherent clinical limitations. This is a procedure with several known complications associated with this route of administration, says Brittni A. Scruggs, M.D., Ph.D., lead author of the study and a vitreoretinal surgeon at Mayo Clinic in Rochester, Minnesota, noting that subretinal delivery can cause localized damage and restrict gene expression to the immediate treatment zone.

Epiretinal Hydrogel Placement Offers Broad Distribution

To address these surgical challenges, researchers in the Retinal Regenerative Medicine Laboratory at Mayo Clinic developed a technique involving epiretinal placement. Instead of piercing underneath the tissue, the therapy is suspended in a specialized fibrin gel and placed directly on the surface of the retina, according to Alan D. Marmorstein, Ph.D.

With this newly developed, alternative approach, the therapy is placed gently on the surface of the retina within a fibrin hydrogel, says Dr. Marmorstein. The hydrogel degrades over the course of a few days, releasing the gene therapy gradually and allowing it to reach a broader area of retinal cells at lower doses. In large animal models, this epiretinal method achieved wide gene expression while generating less inflammation than traditional subretinal injections.

The research team, which includes Dr. Scruggs, Dr. Marmorstein, and Raymond Iezzi Jr., M.D., plans to conduct head-to-head comparisons against existing surgical techniques in disease models to measure potential improvements in visual rescue. Our next step is to test this new method head-to-head with existing techniques in models of retinal disease to see if it can further improve visual rescue, says Dr. Scruggs.