Researchers have demonstrated the ability to deliver a fully functional copy of the CLN3 gene to stem cells of patients with juvenile NCL, an inherited neurodegenerative disease in which a mutation in the CLN3 gene causes early-onset severe central vision loss. The gene therapy restored production of CLN3 protein in the stem cell-derived retinal neurons, as described in an article in Human Gene Therapy.

The article entitled "Using Patient-Specific Induced Pluripotent Stem Cells and Wild-type Mice to Develop a Gene Augmentation-based Strategy to Treat CLN3-associated Retinal Degeneration" is part of a special joint issue on stem cell gene therapy in Human Gene Therapy and Stem Cells & Development guest edited by Luigi Naldini, MD, Scientific Director, San Raffaele Telethon Institute for Gene Therapy, Milan, Italy.

Luke Wiley, Budd Tucker, and coauthors from University of Iowa, Iowa City, describe the gene augmentation method they developed using an adeno-associated virus (AAV2) vector carrying the full-length coding sequence of human CLN3 to deliver the gene to induced pluripotent stem cells (iPSC) derived from patients' fibroblasts. The researchers also demonstrate the safety of AAV2-CLN3, as it produced no toxicity when injected into the retinas of mice. The authors propose that these results serve as proof of principle to support initiation of a clinical trial using AAV-mediated gene augmentation to treat children with CLN3-associated retinal degeneration.

"There are more than 20 distinct genetic diseases that cause blindness. Prior clinical successes with gene therapy for one of these diseases has raised hopes for patients and families affected by other such diseases, " says Editor-in-Chief Terence R. Flotte, MD, Celia and Isaac Haidak Professor of Medical Education and Dean, Provost, and Executive Deputy Chancellor, University of Massachusetts Medical School, Worcester, MA. "This pivotal work from the group at the University of Iowa has shown that one of the most severe degenerative diseases affecting the retina, juvenile NCL, may also be treatable with gene therapy."