Researchers Use Gene Therapy To Restore Hearing In Deaf Mice, Find Out More Here!

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A team of researchers at Harvard Medical School and Boston Children's Hospital reported back in 2015 that they were able to restore rudimentary hearing in genetically deaf mice using gene therapy. The Boston Children's hospital research team recently reports that they have restored a much higher level of hearing - down to 25 decibels, the equivalent of a whisper.

They used an improved gene therapy vector developed at Massachusetts Eye and Ear. Although previous vectors have only been able to penetrate the cochlea's inner hair cells, the first Nature Biotechnology study reveals that a new synthetic vector, "Anc80," is capable of transferring genes to the inaccessible outer hair cells when introduced into the cochlea.

Three Harvard Medical School senior investigators who led the development of Anc80's in 2015 at Mass. Eye and Ear's Grousbeck Gene Therapy Center stated that "We have shown that Anc80 works remarkably well in terms of infecting cells of interest in the inner ear." They believe that many patients will benefit from the technology as more than 100 genes known to cause deafness in humans have already been discovered, according to Science Daily.

The second study, led by Gwenaëlle Géléoc, PhD, of the Department of Otolaryngology and F.M. Kirby Neurobiology Center at Boston Children's hospital, used Anc80 to deliver a specific corrected gene in a mouse model of Usher syndrome - a common genetic form of deaf-blindness that also impairs balance function. The strategy makes Outer hair cells to amplify sound, allowing inner hair cells to send a stronger signal to the brain. It works well and rescues auditory and vestibular function to a level that has never been achieved in the past.

Ushering in gene therapy for deafness, the researchers studied mice with a mutation in Ush1c, the same mutation that causes Usher type 1c in humans which makes a protein called harmonin nonfunctional. Thereby causing the sensory hair cell bundles that receives sound and signal the brain to deteriorate and become disorganized, leading to significant hearing loss.

The inner and outer hair cells in the cochlea started producing normal full-length harmonin, when a corrected Ush1c gene was administered into the inner ears of the mice. The hair cells formed normal bundles which responded to sound waves and then signaled the brain, as measured by electrical recordings.

Amazingly, the deaf mice treated soon after birth began to hear, with the researchers first noting this in a startle box that detects whether mice reacts to sudden loud sounds. It was followed by measuring responses in the auditory regions of the brain, where the researchers found that the mice responded to quieter sounds with 19 out of 25 mice hearing sounds quieter than 80 decibels. Few of them were able to hear sounds as soft as 25-30 decibels, just like normal mice.

According to Daily Mail, the researchers also checked if gene therapy restored balance as patients and mice with Usher 1c also have balance problems caused by hair cell damage in the vestibular organs. They found that eliminated the erratic movements of mice with vestibular dysfunction and enabled the mice to stay on a rotating rod for longer periods without falling off in another test.

However, further study to better understand the technology is necessary before the technology can be used in humans. The shortcomings of the study are that the mice were treated immediately after birth, and hearing/balance were not restored when gene therapy was delayed 10-12 days. But the effects remained for at least six months when treatment is conducted early, with just a slight decline between 6 weeks and 3 months.

Usher syndrome also leads blindness as it causes the light-sensing cells in the retina to gradually deteriorate. While these studies did not check for vision restoration, gene therapy in the eye is already underway for other disorders. The findings of the study are described in two back-to-back papers in Nature Biotechnology.