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Gene modulation method may provide insight on regrowing inner-ear sensory hair cells

Date:
June 11, 2015
Source:
Creighton University
Summary:
An expert in the biology and physiology of the inner ear has developed a method to temporally modify the expression of the retinoblastoma-1 gene in mice. 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.
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A revolutionary new technique in controlling gene expression to aid in the regeneration of other cells has earned a Creighton University researcher a major grant from the National Institutes of Health.

Sonia Rocha-Sanchez, Ph.D., 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 gene in mice. 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 research Rocha-Sanchez published in Frontiers in Cellular Neuroscience in February, the NIH has awarded her $417,399 over two years to continue exploring uses of the 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, who has been at Creighton for eight years. "After sufficient regrowth of those cells, we can return the gene to its previous state, because it is an important gene for the prevention of some cancers."

All mammalian vertebrates, including humans, are born with a limited number of sensory hair cells. 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. Although cochlear implants have revolutionized the auditory field, not all hearing loss patients qualify for the procedure. As such, Rocha-Sanchez said, the development of alternative methods to restore hearing and balance are especially important.

"We are all at risk of losing these cells," she said. "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 said in roughly 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. Soon after publication of the first manuscript on this novel mouse model, Rocha-Sanchez was contacted by researchers interested in utilizing this mouse model on their own research. From Tohoku University in Tokyo, Japan to Stanford University, researchers want to explore the potential of this mouse model for their own research.

In the meantime, Rocha-Sanchez and her team are also continuing to work with the model and see what the implications are for regrowth of the inner-ear cells in the mammalian inner ear.

"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," she said. "Although preliminary, we think the chances are great that this can be, eventually, translated into human therapies."


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Cite This Page:

Creighton University. "Gene modulation method may provide insight on regrowing inner-ear sensory hair cells." ScienceDaily. ScienceDaily, 11 June 2015. <www.sciencedaily.com/releases/2015/06/150611114208.htm>.
Creighton University. (2015, June 11). Gene modulation method may provide insight on regrowing inner-ear sensory hair cells. ScienceDaily. Retrieved May 23, 2017 from www.sciencedaily.com/releases/2015/06/150611114208.htm
Creighton University. "Gene modulation method may provide insight on regrowing inner-ear sensory hair cells." ScienceDaily. www.sciencedaily.com/releases/2015/06/150611114208.htm (accessed May 23, 2017).

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