Towards a genetic treatment for hearing loss
28 August 2008
A new breakthrough suggests that gene therapy may be developed in the future as a treatment for hearing loss. The results of the research by scientists at Oregon Health and Science University are published online this week by the journal Nature.
"One approach to restore auditory function is to replace defective cells with healthy new cells," said John Brigande, Assistant Professor of Otolaryngology at the Oregon Hearing Research Center in the OHSU School of Medicine. "Our work shows that it is possible to produce functional auditory hair cells in the mammalian cochlea."
The researchers specifically focused on the tiny hair cells located in a part of the cochlea called the organ of Corti. It has long been understood that as these hair cells die, hearing loss occurs. A certain number of these cells will malfunction or die naturally leading to gradual, age-related hearing loss in most of the population. Exposure to loud noise, certain medical conditions and ototoxic drugs also add to the risk of losing more sensory hair cells than average and therefore increase the chance of developing more pronounced hearing loss.
Brigande and colleagues were able to produce hair cells by transferring a key gene, called Atoh1 (also known as Math-1), into the developing inner ears of mice. The gene was inserted along with green florescent protein (GFP) which is the molecule that makes a species of jellyfish glow. GFP is often used in research as a "marker" that a scientist can use to determine, in this case, the exact location of the Atoh1 expression. Remarkably, the gene transfer technique resulted in Atoh1 expression in the organ of Corti, where the sensory hair cells form.
Using this method, the researchers were able to trace how the inserted genetic material successfully led to hair cell production, resulting in the appearance of more hair cells than are typically located in the ears of early postnatal mice. Crucially, Dr. Anthony Ricci, Associate Professor of Otolaryngology at the Stanford University School of Medicine, demonstrated that the gene-treated hair cells behave like ordinary hair cells in terms of their electrophysiological properties, meaning that the gene-treated cells appear to be functional.
Andy Forge, Professor of Cell Biology at the University College London Ear Institute says "Although still a long way from the clinic, the work shows that gene therapy is a potential treatment to combat some forms of congenital deafness. With one in two thousand children born deaf because of genetic defects, such a therapy would clearly be of value.
"Work supported by Deafness Research UK to identify the genetic basis of deafness assumes even greater significance."
