A Creighton University researcher has developed a new technique for controlling gene expression to aid in the regeneration of sensory hair cells in the inner ear to potentially restore hearing and balance. According to a recent announcement from the university, a research team led by Sonia M. Rocha-Sanchez, PhD, an associate professor of oral biology in the Creighton School of Dentistry and an expert in the biology and physiology of the inner ear, has developed a method to temporally modify the expression of the retinoblastoma-1 (RB1) gene in mice.
The team reports that modulation of the RB1 gene can allow for the regrowth of cells in the inner ear and potentially restore hearing and balance caused by the loss of sensory hair cells. Previously, only two methods were available for researchers to modulate the expression of the retinoblastoma gene: opening it up to its fullest expression, or completely deleting it. Based on a research article published in the February 23, 2015 edition of Frontiers in Cellular Neuroscience, Rocha-Sanchez has received an NIH grant to continue exploring uses of the cell regeneration technique and its potential translation as a gene therapy option for humans.
“We’ve designed a system where the expression of the retinoblastoma gene can be reduced for a time and we’ve seen the beneficial growth of inner-ear hair cells,” said Rocha-Sanchez. “After sufficient regrowth of those cells, we can return the gene to its previous state.”
All mammalian vertebrates, including humans, are born with a limited number of sensory hair cells, say the researchers. Once lost, these cells are unable to regenerate, leading to hearing loss, deafness, and balance impairment. The modulation of gene expression for just a brief period has shown the potential for significant developments in inner-ear sensory hair cell replacement therapy.
“We are all at risk of losing these cells,” said Rocha-Sanchez. “Genetic deafness affects roughly three out of every 1,000 births. Genetically-induced hearing loss and deafness can also be progressive in nature, worsening as we grow older. And as we age, regardless of any specific genetic predisposition, regular wear and tear of sensory hair cells can cause them to die. Noise is one of the most common causes of hearing loss. If you attend lots of rock ’n’ roll concerts or turn up the volume in your earbuds, you start losing lots of those sensory cells and they can’t be brought back. We’ve also seen that balance is heavily affected by the loss of these cells. Some individuals who have lost a significant amount of sensory hair cells in the vestibular organs, the part of the inner ear controlling balance and equilibrium, are unable to walk on their own two feet any longer.”
Rocha-Sanchez reported that in a two-week period of lessening the expression of the RB1 gene in transgenic mice, inner-ear cells have regrown without adverse side effects previously observed in other retinoblastoma mouse models. Rocha-Sanchez and her team are continuing to work with the model they developed to see what the implications are for regrowth of the inner-ear cells in the mammalian inner ear. And, other researchers have become interested in exploring the potential of Rocha-Sanchez’s mouse model for their own research.
“We’re very excited about what this means for inner-ear research, but also for the other options it opens up in gene modulation crossover and in other areas of research, including cancer research,” Rocha-Sanchez said. “Although preliminary, we think the chances are great that this can be, eventually, translated into human therapies.”
Source: Creighton University, Creighton School of Dentistry; Newswise
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