This time, we're sharing a special blog post from Dr. Steve Gross, who is developing a promising new drug for ADOA at Stoke Therapeutics. On Patient Day, November 1, 2025, he shared inspiring and important new insights. The key discoveries: ADOA patients lose vision over time when reading gray letters; this functional loss even occurs before retinal damage is visible; and researchers can now measure stress within mitochondria. These insights bring us a step closer to treatments, as they allow researchers to measure the effect of a drug with increasing accuracy and precision.
New insights into ADOA from Stoke Therapeutics
Dr. Steve Gross, Senior Medical Director of Clinical Development – Ophthalmology at Stoke Therapeutics, recently spoke at the Cure ADOA Foundation Conference. He shared important updates from the 2025 American Academy of Ophthalmology (AAO) Annual Meeting and explained how these findings will guide the development of potential new treatments—including STK-002, the drug being studied in the recently started OSPREY Phase 1 study.
At the AAO, Prof. Patrick Yu Wai Man presented new two-year results from Stoke's FALCON natural history study—the first longitudinal, prospective study of people with Autosomal Dominant Optic Atrophy (ADOA) caused by loss-of-function OPA1 gene variants. Dr. Gross emphasized how this research deepens our understanding of ADOA and will aid in the development of STK-002.
What we learned from FALCON
The study followed 47 participants in the US, UK, Italy, and Denmark for 24 months. Key findings include:
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- Gradual progression:
High-contrast visual acuity remained stable for two years, confirming that ADOA changes slowly.
- Gradual progression:
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- Sensitive early markers:
Among participants who completed low-contrast vision tests, about one in four showed vision loss — subtle declines that would go unnoticed in standard eye exams.
- Sensitive early markers:
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- Functional decline precedes structural loss:
Even when mild decline in visual function occurs, retinal anatomy remains largely stable.
- Functional decline precedes structural loss:
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- Demonstrated mitochondrial stress:
Using a novel imaging tool (the OcuMet Beacon), researchers confirmed increased mitochondrial stress in ADOA, underscoring the role of mitochondrial health in disease progression.
- Demonstrated mitochondrial stress:
Preview: From FALCON to OSPREY
The insights from FALCON form the basis for the clinical development of STK-002, an antisense oligonucleotide (ASO) therapy designed to increase production of the healthy OPA1 protein in patients who carry one normal and one defective copy of the gene.
Early laboratory studies have shown that STK-002 reaches retinal ganglion cells and increases OPA1 protein levels. Stoke has now started OSPREY, a Phase 1 clinical study investigating the safety of the therapy and early effects on vision over a 48-week period.
Why this is important
These developments represent a significant step toward a possible treatment for ADOA. With each study, researchers discover new ways to measure the effects of this inherited optic nerve disorder—and ultimately slow or even reverse them.
The progress shared at the Cure ADOA Foundation Conference offers new hope for the ADOA community and the families working together to advance this research.
More information about Falcon can be found here in this presentation from the NANOS conference of March 2025.
* Dr. Steve Gross, MD, is a full-time employee of Stoke Therapeutics, Inc. and owns stock in the company. The information in this text is for informational and educational purposes only. STK-002 has been granted orphan drug designation by the FDA as a potential new treatment for ADOA. A Phase 1 study (OSPREY) of STK-002 is currently underway in people with ADOA to assess its safety, potential side effects, and how the body processes the study drug.
