Revitalizing Vision: Metabolome Rejuvenation Can Slow Retinal Degeneration

Key Takeaways

  • Scientists are designing a gene therapy with the potential to treat retinitis pigmentosa (RP) patients regardless of the underlying genetic defect.
  • The experimental therapy, which has been tested in mice, corrects a metabolic error in the eye’s light-sensing cells that is common to most forms of the disease.

Gene therapy may be the best hope for curing RP, an inherited condition that usually leads to severe vision loss and blinds 1.5 million people worldwide. But there’s a huge obstacle: RP can be caused by mutations in over 80 different genes. To treat most RP patients with gene therapy, researchers would have to create a therapy for each gene—an impractical task using current gene therapy strategies.

A more universal treatment may be forthcoming. Using CRISPR-based genome engineering, scientists at Columbia University Vagelos College of Physicians and Surgeons are designing a gene therapy with the potential to treat RP patients regardless of the underlying genetic defect. The experimental therapy—which is still several years away from testing in people—corrects a metabolic error in the eye’s light-sensing cells that is common to most forms of the disease. In a study published in Cell Reports Medicine, the genome engineers report that their CRISPR-based gene therapy can delay the progression of RP for about one month in mouse models of the disease, equivalent to about 10 years in humans. 

The models included two genetically distinct types of RP, suggesting that the therapy would work for many forms of the disorder. In contrast, the lone FDA-approved RP gene therapy is suitable only for a few hundred patients in the United States whose condition is caused by the gene encoding the RPE65 isomerase. “A universal precision metabolome rejuvenation would be a vast improvement over the limited options now available to most RP patients, which do little to prevent blindness,” says study leader Stephen Tsang, MD, Ph.D. 

The next step for the proposed gene therapy is to validate the mechanism of action with the lab’s established rodent models of degeneration before translating these studies into a larger animal model with an eye structure that more closely resembles that of a human. “These studies will provide a clearer understanding of the potential of precision rejuvenating therapy and will enable a more comprehensive safety assessment to be conducted,” Tsang said.

Source: Columbia University Irving Medical Center, Medical Xpress, March 21, 2024; see source article