Latest outcomes in ophthalmology build on 2007 breakthrough at PAMELA, predecessor to PEARL

In a groundbreaking medical advance, a team at Moorfields Eye Hospital has successfully restored vision in children with a rare genetic condition, marking a significant leap in the field of ophthalmological gene therapy. Led by Professors James Bainbridge and Michel Michaelides, the group used a newly refined genetic replacement technique that has allowed toddlers to gain sight—an achievement building on years of pioneering work.

Much of the groundwork for this recent success was laid in 2007–2008, during an earlier study that tested gene therapy in young adults. At that time, the team took advantage of the then-new PAMELA facility (PEARL’s predecessor), where researchers could create carefully controlled yet realistic lighting and navigation scenarios. By analysing participants’ navigation abilities before and after the genetic intervention, the Moorfields team was able to confirm significant improvements in visual function under real-world conditions.

Now, the arrival of the PEARL facility takes this concept even further. PEARL allows researchers to construct, customise, and reproduce intricate “ecological mazes” that mimic typical street environments. This degree of control and repeatability is crucial not only for understanding the effectiveness of a one-time gene therapy intervention but also for assessing changes in patient performance over the long term. By reshaping these mazes or introducing new elements, researchers can ensure that study participants are navigating new or evolving routes—providing an even more accurate test of improved vision in a real-world setting.

“Your work at PAMELA was critical in establishing an important new outcome measure for genetic eye disease,” said Professor Bainbridge, emphasising how the facility’s ability to simulate real-life environments allowed for the creation of new, meaningful measures of patient improvement.

Although this innovation has focused on treating genetic eye diseases so far, the flexibility of the PEARL facility opens up promising possibilities for research into a broad range of conditions. Future therapies, for instance, might target people with dementia, hearing loss, or neurodivergent individuals—groups for whom interactions with the environment are crucial to daily living and often difficult to study. Researchers see PEARL as the ideal setting to fine-tune environments and interventions that can foster greater accessibility and comfort.

With the publication of the team’s new study in The Lancet—and the evident success of toddlers now able to see where they once could not—this longstanding research journey has gained fresh momentum. The remarkable outcomes not only deliver immediate hope to families but hint at an expansive future for using controlled ecological environments to revolutionise clinical therapies.

References

Michel Michaelides*, Yannik Laich*, Sui Chien Wong, Ngozi Oluonye, Serena Zaman, Neruban Kumaran, Angelos Kalitzeos, Harry Petrushkin, Michalis Georgiou, Vijay Tailor, Marc Pabst, Kim Staeubli, Roni O Maimon-Mor, Peter R Jones, Steven H Scholte, Anastasios Georgiadis, Jacqueline van der Spuy, Stuart Naylor, Alexandria Forbes, Tessa M Dekker, Eugene R Arulmuthu, Alexander J Smith, Robin R Ali, James W B Bainbridge (2025), Gene therapy in children with AIPL1-associated severe retinal dystrophy: an open-label, first-in-human interventional study, The Lancet, 405, pp 648-657

Bainbridge J, Smith A, Barker S, Robbie S, Henderson R, Balaggan K, Viswanathan A, Holder G, Stockman A, Tyler N, Petersen-Jones S, Bhattacharya S, Thrasher A, Fitzke F, Carter B, Rubin G, Moore A, Ali R (2008) Effect of gene therapy on visual function in Leber's congenital amaurosis, New England Journal of Medicine, 358(21) 2231-2239