Unlocking the Future: How Gene Therapy is Restoring Vision!
gene therapy improves vision
Gene Therapy Transforms Vision: 10,000 Times Better
Patients affected by a rare genetic condition impairing their vision experienced swift and lasting enhancements in sight over the course of a year-long investigation.
Individuals suffering from an uncommon hereditary disorder, which induces significant vision loss during early childhood, saw an astounding 100-fold improvement in their sight following gene therapy designed to address the specific genetic mutation.
Some patients, particularly those who received the highest dosage, witnessed a remarkable 10,000-fold improvement, according to researchers from the Perelman School of Medicine at the University of Pennsylvania. These experts co-led the clinical trial, recently published in The Lancet.
“That 10,000-fold enhancement is akin to the difference between seeing one’s surroundings under dim moonlight, as opposed to needing bright indoor lighting prior to treatment,” explained the study’s lead author, Dr. Artur Cideciyan, a research professor of Ophthalmology and co-director of the Center for Hereditary Retinal Degenerations. “One patient, for instance, reported navigating outdoors at midnight with only the light of a bonfire for the very first time.”
Fifteen individuals, including three children, participated in this Phase 1/2 trial. All had Leber congenital amaurosis, caused by mutations in the GUCY2D gene, critical for the production of proteins essential to vision. This specific condition, known as LCA1, afflicts fewer than 100,000 people globally and leads to severe vision impairment as early as infancy.
The trial’s participants suffered from pronounced vision loss, with their best recorded vision at 20/80 or worse, meaning objects seen clearly at 80 feet by the average person could only be seen at 20 feet by these patients.
Corrective lenses provided limited relief, as glasses address optical focusing issues but cannot rectify the genetic retinal diseases such as LCA1.
gene therapy improves vision: Therapy Application and Results
The trial explored varying doses of gene therapy, known as ATSN-101, derived from the AAV5 microorganism and injected beneath the retina. Initially, groups of three adults received one of three dosages—low, medium, and high. The dosages were gradually increased following safety evaluations. The second phase of the study administered the highest dosage to a new adult cohort and a pediatric group after previous safety assessments.
Notable improvements were observed swiftly, often within the first month, and persisted for at least 12 months. Monitoring of the patients remains ongoing.
Three out of six high-dosage recipients, when tested on a mobility course with different lighting conditions, achieved the highest possible score. Additional tests involved eye charts or measuring the faintest flashes of light perceived in a dark environment.
Of the nine high-dosage patients, two experienced the extraordinary 10,000-fold improvement in vision.
“Despite predicting significant potential for vision improvement in LCA1 patients, we were uncertain how receptive their photoreceptors would be after decades of blindness,” Cideciyan remarked. “The success of this multi-center trial highlights the dramatic efficacy of gene therapy.”
gene therapy improves vision: Safety and Side Effects
The primary objective of the study was to determine the safety of the gene therapy across different dosage levels. Some participants experienced side effects, but most were linked to the surgical procedure itself. The most frequent complication was conjunctival hemorrhage, a rupture of small blood vessels beneath the eye’s clear surface, which healed on its own.
Two patients developed eye inflammation, which was treated with steroids. No serious side effects related to the study drug were reported.
This breakthrough follows another successful ophthalmology trial at Penn earlier in 2024, which restored sight in patients suffering from a different form of LCA. That trial used CRISPR-Cas9 gene editing to treat mutations in the CEP290 gene and was co-led by Dr. Tomas S. Aleman, one of the authors of the current study. It marked the first time children were involved in gene editing research.
“The success of these clinical trials offers hope for treating around 20% of infantile blindness caused by inherited retinal disorders,” said Aleman.
“Our focus is now on refining these treatments and addressing earlier stages of these conditions once safety is ensured. We’re optimistic that similar techniques could yield equally promising results for other forms of congenital retinal blindness.”
The next step toward approval of this experimental therapy for clinical use requires another trial. In this phase, participants will be randomly assigned treatment dosages without knowing what they receive, eliminating any potential bias in the outcomes.
Reference
“Safety and efficacy of ATSN-101 in patients with Leber congenital amaurosis caused by biallelic mutations in GUCY2D: a phase 1/2, multicentre, open-label, unilateral dose escalation study” by Paul Yang, Laura P Pardon, Allen C Ho, Andreas K Lauer, Dan Yoon, Shannon E Boye, Sanford L Boye, Alejandro J Roman, Vivian Wu, Alexandra V Garafalo, Alexander Sumaroka, Malgorzata Swider, Iryna Viarbitskaya, Tomas S Aleman, Mark E Pennesi, Christine N Kay, Kenji P Fujita, and Artur V Cideciyan. Published in The Lancet.
DOI: 10.1016/S0140-6736(24)01447-8
This research was funded by Atsena Therapeutics, Inc. Two of the paper’s authors, Dr. Andres K. Lauer and Dr. Mark Pennesi, serve on the company’s clinical and scientific advisory board.
