Gene Therapy: What’s to Come?

Modern Retina Digital EditionModern Retina Fall 2023
Volume 3
Issue 3

With a robust pipeline, new hope for Stargardt disease and retinitis pigmentosa may be on the horizon.


With a robust pipeline, new hope for Stargardt disease and retinitis pigmentosa may be on the horizon. (Image Credit: ©RFBSIP -

In the 20 years since the human genome project was completed, allowing humanity for the first time to fully unlock our DNA, we have made astounding progress. Today, we understand better than ever the value of each strand of DNA and the role genes play in who we are and how we live. Of course, there is much more to discover.

Among those discoveries, we can find hope that conditions that do not yet have a treatment may soon meet their match, whether that be in the form of an injection, a pill, or even an eye drop. Research in gene therapy treatments is bringing forward new solutions for 2 of ophthalmology’s toughest conditions: Stargardt disease and retinitis pigmentosa (RP).

Pipeline for stargardt disease

Thanks to decades of research, we know that Stargardt disease is caused by mutations on the ABCA4 or ELOVEL4 genes and affects an estimated 1 in 10,000 individuals globally, often presenting in childhood or adolescence.1 This understanding has pharmaceutical companies looking to stop the progression of the disease through novel treatments, preserving the sight of hundreds of thousands of people around the world.


At the 2023 American Society of Retina Specialists (ASRS) Annual Scientific Meeting, Michael Singer, MD, a retinal specialist with Medical Center Ophthalmology Associates in San Antonio, Texas, shared insights with Modern Retina on the phase 2 STARLIGHT study (NCT05417126). It was a small proof-of-concept study in which 6 patients positive for ABCA4 received MCO-010, a multichromatic opsin that is gene agnostic and is produced by Nanoscope Therapeutics. Singer noted in the interview that the patients had not received any other treatment and that they “saw significant improvements in terms of their visual field, full questionnaires, and visual acuity.”2 This therapeutic is also being evaluated for RP in the ongoing
phase 2 RESTORE trial (NCT04945772).

Watch the interview with Michael Singer, MD, on


The search for a solution to Stargardt disease is a global one. The phase 3 DRAGON study (NCT05244304) is evaluating tinlarebant (LBS-008), which is described by Belite Bio Inc as “an oral, once-daily retinol binding protein 4 (RBP4) antagonist designed to lower levels of ocular vitamin-A based toxins implicated in [Stargardt disease].”3 The DRAGON study is taking place at sites in the United States, United Kingdom, Germany, France, Belgium, Switzerland, Netherlands, China, Hong Kong, Taiwan, and Australia. Enrollment was completed in July 2023 with 90 adolescent participants randomly assigned 2:1 to tinlarebant or placebo.3

Tinlarebant has been granted fast track and rare pediatric disease designations in the US, and orphan drug designation in both the United States and Europe. At this time, there are no FDA-approved treatments for Stargardt disease. Interim safety and efficacy data from the DRAGON study are expected in mid-2024.3


Like Stargardt disease, RP is an inherited retinal condition that over time progresses to blindness. The disease results from mutations in 1 of more than 150 genes, affecting approximately 1 in 4000 individuals globally and more than 100,000 patients in the United States. Of those with RP, 50% of patients are not qualified to drive by age 37 and are legally blind by age 55.1

The prevalence of this condition and the seriousness of its progressions highlight why researchers and ophthalmologists around the globe are keen to assist patients with RP to preserve their remaining sight or potentially reverse the disease’s effects. Through advancing pharmaceutical treatments, there may soon be more tools in the ophthalmic toolbox to treat this genetic condition.


One potential treatment for RP, which is being developed by Kiora Pharmaceuticals, is molecular photoswitches. Kiora’s KIO-301 works by targeting retinal ganglion cells (RGCs), turning them into light-sensing cells. RGCs are preserved in conditions such as RP and Stargardt disease, which, according to Kiora, makes them “an ideal downstream target that can bypass dead photoreceptors to process light and signal the brain.”4

Although this particular treatment is not a gene therapy, it could be used in conjunction with future gene therapies that may be developed and may serve as a more cost-effective option for patients, helping the treatment to reach more of those with the condition. Kiora is conducting the phase 1b ABACUS clinical study (NCT05282953) with KIO-301 in Australia and hopes to complete this phase in November 2023.5


As with many of the treatments in development, MCO-010 (Nanoscope) is simultaneously being evaluated for the treatment of Stargardt disease and RP. In April 2023, topline results from the RESTORE trial (NCT04945772) for the compound as a treatment for patients with RP were presented at the 2023 Association for Research in Vision and Ophthalmology Annual Meeting. A Nanoscope news release noted that “100% (18/18) MCO-010 patients experienced a clinically meaningful improvement in vision-guided mobility (MLYMT), near-field object recognition (MLSDT) or visual acuity (BCVA) (P = .007 vs sham).”6


Among the many genes that can cause RP, PDE6B may have met its match. In May 2023, Coave Therapeutics shared positive 12-month results from a phase 1/2 trial of CTx-PDE6b (NCT03328130). The treatment is designed specifically for cases of RP resulting from biallelic mutations on PDE6B.7 The company’s news release noted that the treatment was well-tolerated and researchers saw positive efficacy results.7

Take Home

The field of gene therapy (and beyond) is working to bring new solutions forward, fostering hope in providers and patients that there will soon be help for these conditions. New trials and treatments progress through pipelines and meet end points around the globe. To keep an eye on it all would be difficult, if not impossible. However, with each new announcement, we can collectively see an exciting, remarkable future, and more importantly, those with Stargardt disease or RP will be able to see that future as well. •

  1. Inherited retinal diseases. Kiora Pharmaceuticals. Accessed August 22, 2023.
  2. Crago SM, Hutton D. ASRS 2023: Michael Singer, MD, provides details on the Starlight study for Stargardt disease.Modern Retina. August 6, 2023. Accessed August 22, 2023.
  3. Belite Bio completes enrollment in pivotal global phase 3 DRAGON trial evaluating oral tinlarebant for Stargardt disease. News release. Belite Bio, Inc. July 24, 2023. Accessed August 22, 2023.
  4. ‌KIO-301. Kiora Pharmaceuticals. Accessed August 22, 2023.
  5. Let there be light: a spotlight on Kiora’s flagship product, KIO-301, which aims to restore vision for patients with a rare inherited retinal disease. Kiora Pharmaceuticals. Accessed August 22, 2023.
  6. Nanoscope Therapeutics announces presentation of key results from phase 2b RESTORE trial of MCO-010 for the treatment of retinitis pigmentosa at the ARVO Annual Meeting. News release. Nanoscope Therapeutics. April 27, 2023. Accessed August 22, 2023.
  7. Coave Therapeutics announces positive 12-months data from ongoing phase I/II clinical trial of CTx-PDE6b in patients with retinitis pigmentosa caused by bi-allelic mutations in PDE6b. News release. Coave Therapeutics. May 31, 2023. Accessed August 22, 2023.
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