The Foundation Fighting Blindness (FFB) is launching a multi-million-dollar natural history study on gyrate atrophy (GYA) to serve as a basis for future research.
Why GYA?
As the world’s leading private funder of retinal disease research, the FFB's focus on GYA fits its ongoing efforts to uncover potential treatments for inherited retinal diseases (IRDs).
GYA—a progressive retinal disease that leads to night blindness and peripheral vision loss, as well as the potential for severe childhood-onset myopia—is caused by mutations within the ornithine aminotransferase (OAT) gene.
How is it normally treated?
GYA patients can follow an arginine-restricted (low-natural protein) diet in order to reduce arginine intake and slow retinal degeneration progression.
However, such a diet is extremely restrictive and can often be difficult for patients to follow.
As an alternative, according to FFB, a gene therapy approach may help to “avoid the need for restrictive dietary control and lead to better vision outcomes over the long term.”
Which brings us to this study?
Yes! The Gyrate Atrophy Ocular and Systemic Study (GYROS) study (NCT05312736) is expected to follow 45 participants diagnosed with GA for 4 years across 12 clinical research sites.
All site locations will be from the FFB’s Clinical Consortium; the study itself is being sponsored by the Jaeb Center for Health Research, based in Tampa, Florida.
The purpose: To determine the design of future GYA clinical trials by performing imaging and visual function tests to better understand how the condition affects the retina and rate of disease progression.
Break it down for me.
Participants will be divided into three vision cohorts:
- Vision cohort 1
- Visual acuity (VA) Early Treatment Diabetic Retinopathy Study (ETDRS) letter score of 54+
- Visual field (VF) diameter +10° in every meridian of the central field
- Vision cohort 2
- VA ETDRS letter score of 19-53 or VA ETDRS letter score of 54+
- Vision cohort 3
- VA ETDRS letter score of 18 or less
And what’s being measured?
Primary outcomes include characterized change using a measurement of progression of the area of preserved retina, as measured via:
- Wide-field fundus autofluorescence (FAF)
- Wide-field color photography
See here for other primary and secondary outcome measures, all measured at baseline and every year until study completion (4 years total).
And who’s leading it?
Lead investigators include:
- Mandeep S. Singh, MBBS, MD, PhD; Andreas C. Dracopoulos Professor of OphthalmologyAssociate Professor of Ophthalmology and Genetic Medicine, Wilmer Eye Institute
- David Valle, MD; professor of Genetic Medicine and former director of the McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University
To note, both ophthalmologists are developing a systemically-delivered gene therapy for GYA in collaboration with Jefferson Doyle, MBBCh, MD, PhD, MHS, of the Wilmer Eye Institute.
How is it being funded?
Per FFB, three groups are collaborating to provide a total of $3.5 million in funding:
- $1.8 million from the FFB
- $1.6 million from the FDA
- $1.9 million from other non-government sources
Additionally, a nonprofit research and patient advocacy group called Conquering Gyrate Atrophy is contributing $100,000.
And the significance?
According to Todd Durham, PhD, FFB’s senior vice president of clinical and outcomes research: “GYROS results will be essential to the design and launch of the planned gene therapy clinical trial, and ultimately, getting a vision-saving treatment out to the people who need it.”
Lastly … how long is this study?
Per Clinical Trials, the study is slated to conclude in January 2028.