A research team from the Institute of Molecular and Clinical Ophthalmology, Basel, Switzerland, has developed a technique to edit genes, demonstrating its potential application in curing Stargardt disease, a rare genetic eye condition leading to vision loss.
Stargardt disease, also known as Stargardt macular degeneration, is an inherited condition that causes progressive vision loss primarily in children and young adults. The disease typically affects both eyes and is characterized by an accumulation of lipofuscin, a yellowish-brown pigment, in the macula, the central part of the retina responsible for clear vision.
The condition is commonly attributed to mutations in the ABCA4 gene, which regulates the body's use of Vitamin A. Currently, no cure exists for Stargardt disease.
The research team, in collaboration with scientists from Beam Therapeutics, developed a highly optimized adenine base editor—a genome editing tool that facilitates precise DNA modifications. This tool was delivered into the retina via an adeno-associated viral vector (AAV), which does not typically integrate into the cell's genome. The study aimed to correct the mutation in the ABCA4 gene.
The findings were published in the journal Nature Medicine, stating, "The resulting gene therapy vectors achieved high levels of gene correction in mutation-carrying mice and in female nonhuman primates... which has the potential to translate to a clinical benefit. No off-target editing was detectable... The high editing rates in primates show promise for efficient gene editing in other ocular diseases that are targetable by base editing."
A September 2023 study from the L. V. Prasad Eye Institute, Hyderabad, reported that Stargardt disease is more prevalent in males, presenting during the second decade of life. The estimated prevalence ranges from 1 in 8000 to 10,000 individuals, often leading to legal blindness.
Among 1,964 patients studied, 10.79% had a family history of Stargardt disease, and 10.69% had documented parental consanguinity. Mohan Rajan, chairperson and medical director of Rajan Eye Care Hospital in Chennai, noted that while hereditary conditions remain challenging in ophthalmology, gene therapy represents a promising future.
S. Soundari, medical director at Dr. Agarwal's Eye Hospital, emphasized the importance of genetic editing for inherited eye diseases and mentioned a partnership with MedGenome to analyze genetic conditions. The L. V. Prasad Eye Institute's research also indicated that stem cell therapy and gene replacement are emerging therapeutic options, calling for a review of policies regarding Stargardt disease management.