Gene Therapy Successful in Usher Syndrome Type 2D Model
August 25, 2011 - Researchers from the University of Utah have used gene therapy to correct the disease-causing genetic defect in the retinas of mice with Usher syndrome type 2D (USH 2D), a form of combined deafness and blindness in humans. While more laboratory work needs to be done, the advancement is an important step toward moving the treatment into a clinical trial.
Usher syndrome is an inherited condition that causes defects in the function of cilia, tiny hair-like structures that act like a transportation system for proteins and biochemicals essential to the proper functioning of photoreceptors and cells of the inner ear. In people with USH 2D, a genetic defect leads to dysfunction of the cilia and, ultimately, vision and hearing loss.
Led by Dr. Jun Yang, the Foundation-funded research team developed a safe, manmade virus to deliver copies of normal USH 2D genes to the photoreceptors of the affected mice. The treatment was injected under the retina where it was absorbed by the photoreceptors. Tests revealed that copies of the therapeutic USH 2D gene reached photoreceptors and restored function of the cilia.
The virus used for therapy delivery – an adeno-associated virus, or AAV – is similar to AAVs used in other gene therapy lab studies and clinical trials. One example is the series of landmark clinical trials that have restored some vision in more than 40 children and young adults with the early-onset retinal disease known as Leber congenital amaurosis.
Dr. Yang said that while the treatment restored ciliary function, retinal degeneration and vision loss in the USH 2D mouse model doesn’t occur until 28 months, which is old for mice. So she and her team are developing mice that live for at least that long to verify the treatment prevents vision loss.
Usher syndrome affects as many as 50,000 people in the United States and hundreds of thousands around the world. There are three primary types of the disease — Usher syndrome type 1, 2 and 3 — and several genetic variations, represented by letters. People with USH 2D generally have moderate, non-progressive hearing loss at birth and variable, progressive vision loss from retinitis pigmentosa that becomes apparent in adolescence or adulthood. |
