January 8, 2025, was no ordinary day in the world of gene therapy for inherited retinal diseases (IRDs)—it was a triple milestone moment.
In just 24 hours, three groundbreaking stories emerged, each offering new possibilities for patients living with these rare and challenging conditions. A cutting-edge base editing therapy is lighting the way for Stargardt disease, a promising treatment for retinitis pigmentosa (RP) is leaping through clinical milestones, and a novel X-linked retinoschisis (XLRS) therapy is advancing into its next trial phase. It’s a big moment for the intersection of science, sight and hope.
Gene editing breakthrough for Stargardt disease
A new gene editing therapy has shown significant promise in addressing Stargardt disease, a leading cause of inherited macular degeneration, according to research published in Nature Medicine.1 The study highlights the use of base editing, a precision gene-editing tool, to correct a common genetic mutation linked to the disease.
✨Breakthrough: IOB & @BeamTx develop efficient gene editing for Stargardt disease. Published in @NatureMedicine, the study shows promise in halting vision loss.
— IOB.ch (@IOB_ch) January 8, 2025
Watch the full movie on: https://t.co/cuHHidYhAT #GeneEditing #VisionResearch #IOBBasel #EyeHealth #Optogenetics pic.twitter.com/oECwhTGz0a
A video on Stargardt’s disease and the development of the new gene editing therapy. Video courtesy of IOB.
The research, led by Dr. Bence György and Dr. Botond Roska of the Institute of Molecular and Clinical Ophthalmology Basel (IOB; Switzerland), in collaboration with Beam Therapeutics (Massachusetts, USA) scientists Dr. David Bryson and Dr. Giuseppe Ciaramella, focuses on correcting the ABCA4 gene mutation using adenine base editors delivered via adeno-associated viral vectors (AAVs).
“Our approach achieved remarkably high levels of gene correction,” stated Dr. György in a news release. “We observed average editing rates of 75% in cone cells and 87% in retinal pigment epithelial cells. These results far exceed what we believe is necessary to provide clinical benefit to patients.”
The study demonstrated the effectiveness of this method across multiple models, including human retinal organoids and adult human retinal tissues, as well as in nonhuman primates. “We are very encouraged to observe this level of potency in these relevant models at clinically relevant doses,” said Dr. Bryson.
Safety was also a focus of the research. Extensive testing revealed no off-target editing in the retina or other tissues, which study co-author Alissa Muller emphasized is crucial for therapy development. “This is crucial for the development of a safe and effective therapy,” Muller explained.
Beyond Stargardt disease, the base editing approach may have potential applications in treating other IRDs caused by similar mutations. Dr. Roska underscored the broader implications of this research, stating, “This work exemplifies a key goal of IOB: combining our deep understanding of retinal biology and vision with breakthrough technologies to develop novel therapies for vision loss.”
Future steps may include further safety testing and preparation for clinical trials. If successful, the therapy could offer hope to thousands of individuals affected by Stargardt disease and related conditions.
FDA recognition and Phase Ib dose escalation approved for RP gene therapy
ViGeneron (Munich, Germany), a clinical-stage gene therapy company, announced two significant milestones in its development of VG901, a novel treatment for RP caused by mutations in the CNGA1 gene. The U.S. Food and Drug Administration (FDA) has granted Rare Pediatric Disease Designation (RPDD) to VG901, and an independent Data Safety Monitoring Board (DSMB) has unanimously approved dose escalation in the therapy’s ongoing Phase Ib clinical trial.
The FDA’s RPDD recognizes the urgent need for therapies targeting rare pediatric diseases like RP caused by CNGA1 mutations. This designation makes ViGeneron eligible to potentially secure a Priority Review Voucher (PRV) upon VG901’s marketing approval. PRVs expedite FDA review processes and can be used for other drug candidates or sold to other companies.
“This RPDD recognition from the FDA highlights the significant unmet medical need in retinitis pigmentosa and underscores VG901’s therapeutic potential as the first-in-class and only clinical-stage therapy targeting retinitis pigmentosa associated with mutations in the CNGA1 gene,” said Dr. Caroline Man Xu, co-founder and CEO of ViGeneron, in a news release.
In addition to this regulatory milestone, the DSMB’s unanimous recommendation allows ViGeneron to advance to higher-dose cohorts in its Phase Ib clinical trial. Dr. Bart P. Leroy, chair of the DSMB and head of the Department of Ophthalmology at Ghent University Hospital, noted, “No dose-limiting adverse events related to VG901 have been reported in the first-dose cohort to date. This marks a critical step toward advancing to the higher dose and represents an important milestone in its clinical development.”
The ongoing trial is evaluating the safety and preliminary efficacy of VG901, which delivers the functional CNGA1 gene to retinal photoreceptor cells via intravitreal injection using ViGeneron’s proprietary vgAAV vector platform.
Atsena advances trial for XLRS gene therapy
Atsena Therapeutics (North Carolina, USA), a clinical-stage gene therapy company, has announced the initiation of Part B of its Phase I/II LIGHTHOUSE study. The trial is evaluating ATSN-201, a novel gene therapy, for the treatment of XLRS, a rare inherited retinal disease that primarily affects males and leads to vision loss.
“We are pleased to initiate Part B of the LIGHTHOUSE study of ATSN-201 following successful enrollment and dosing of Part A,” said Atsena CEO Patrick Ritschel in a news release. “The functional and structural improvements seen in Part A validate our novel AAV.SPR spreading capsid.”
The LIGHTHOUSE study’s Part A assessed the safety and tolerability of three doses of ATSN-201 delivered via subretinal injection. Following a review of early safety data, the Data Monitoring Committee approved moving to Part B with a dose of 1.0E11 vg/mL, which showed an optimal balance of tolerability and efficacy.
Part B of the trial will evaluate nine adults and three pediatric patients across multiple sites. The adult cohort will include three groups: low volume, high volume and a control group, with the latter observed off-therapy for one year before having the option to receive treatment. The pediatric cohort will be treated after initial data from adult participants are reviewed. Safety and efficacy measures include microperimetry, visual acuity and macular structure assessments.
“A major benefit of ATSN-201 is that it does not need to be precisely placed underneath a specific retinal region,” explained Dr. Kenji Fujita, chief medical officer at Atsena. “This gives surgeons more discretion regarding bleb placement during subretinal surgery and allows for safe delivery of the healthy gene to the critical portion of the retina.”
ATSN-201 utilizes AAV.SPR, Atsena’s proprietary spreading capsid, to achieve therapeutic levels of gene expression in the central retina without requiring surgical detachment. This approach addresses the challenges posed by schisis cavities that dominate XLRS patient retinas.
The FDA has granted ATSN-201 both Orphan Drug and Rare Pediatric Disease designations, emphasizing the need for a therapeutic option for this condition.
Reference
- Muller A, Sullivan J, Schwarzer W, et al. High-efficiency base editing in the retina in primates and human tissues. Nat Med. 2025 Jan 8 [Epub ahead of print].
