The cochlear hair cells of humans and other mammals–unlike some animal species (like birds for example)–cannot be restored after damage. Recent research has indicated, however, that manipulation of signaling pathways could lead to hair cell regeneration.
Using a sustained-release formulation of small interfering RNAs (siRNAs) delivered via nanoparticles into the cochlea of noise-injured guinea pigs, researchers observed significant hair cell restoration and hearing recovery across a broad frequency range.
The findings were recently published in the journal Molecular Therapy.
Cochlear Hair Cell Regeneration
Richard Kopke, MD, FACS
CEO of Hough Ear Institute
As noted in The Scientist magazine, ENT physician and researcher, Dr. Richard Kopke, and colleagues previously showed in 2013 that they could regenerate hair cells in cultured mouse cochlea. The strategy behind the research involved using nanoparticles carrying siRNAs targeting Hes1, which is activated following cochlear hair cell damage in mammals, and is known to inhibit the expression of genes that are necessary for hair cell differentiation. Thus, the hypothesis was that interrupting Hes1 activity could allow the cells to regenerate.
To test their siRNA therapeutic strategy in vivo, Kopke and colleagues exposed anesthetized guinea pigs to constant loud noise for three hours. Then they tested the animals’ hearing (via Auditory Brainstem Response) and randomly divided them into two groups: 11 guinea pigs received a 24-hour infusion of nanoparticles containing Hes1-targeted siRNAs, and nine got a control infusion of siRNAs with no expected activity.
The nanoparticles carrying the sequences were delivered directly to the cochlea three days after noise exposure.
Compared to the control (left), animals treated with siRNA targeting Hes1 show the presence of substantially more hair cells. Inner and outer hair cells (IHC and OHC) are labeled in green, stereocilia in yellow, and nuclei in blue. Arrows indicate ectopic hair cells. Images courtesy The Scientist via Molecular Therapy
Three weeks following the intervention, treated guinea pigs were found to have recovered the ability to hear some loud noises and the recovery was sustained until the end of the nine week study. The treated animals were found to have less cochlear hair cell loss, compared with the control group, along with the presence of “ectopic and immature hair cells” which were described as signs of regeneration by the study authors.
The researchers believe their method of delivering siHes1 to the cochlea represents a promising approach to regeneration of “functional and sustainable mammalian hair cells in vivo”. In the future they plan to investigate the effectiveness of their treatment over longer periods of time than the current study and will also examine effects of different dose rates and delivery techniques. Their ultimate hope is that the research will eventually lead to an effective clinical treatment for people with hearing loss.
Source: The Scientist, Molecular Therapy
