Sounds good. New auditory neurons grew in a deaf guinea pig given DNA for a growth factor (above), but not in the same animal’s untreated ear.

Sounds good. New auditory neurons grew in a deaf guinea pig given DNA for a growth factor (above), but not in the same animal’s untreated ear.

UNSW Translational Neuroscience Facility

Implant Injects DNA Into Ear, Improves Hearing

Many people with profound hearing loss have been helped by devices called cochlear implants, but their hearing is still far from normal. They often have trouble distinguishing different musical pitches, for example, or hearing a conversation in a noisy room. Now, researchers have found a clever way of using cochlear implants to deliver new genes into the ear—a therapy that, in guinea pigs, dramatically improves hearing.

The most common cause of deafness is loss of the tiny hair cells within the cochlea, a hollow, spiral structure in the inner ear that translates sounds into nerve impulses. Hearing aids that merely amplify sounds don't help people who have lost these hair cells. So since the 1970s, more than 320,000 children and adults around the world who are deaf or severely hard of hearing have received cochlear implants. Instead of relying on hair cells, the device converts sounds into electrical impulses, then uses electrodes to relay these signals to the auditory nerve leading to the brain. But because the auditory nerve lies buried within tissue, the implants don't work as well as they could if the electrodes were closer to the nerve.

Some researchers have spurred new neurons to grow inside the cochlea using a protein called a growth factor. They have pumped the growth factor into the inner ear, or used a virus to deliver a gene that codes for it into cells. But pumped-in growth factor doesn't work for long unless it is replenished. And viral gene therapy doesn’t always put the gene in the right cells and carries risks, such as a reaction from the immune system to the virus.

Graduate student Jeremy Pinyon and colleagues in the laboratory of neuroscientist Gary Housley at the University of New South Wales in Sydney, Australia, tested a different kind of gene therapy on guinea pigs made deaf with a drug that kills cochlear hair cells. The researchers created loops of DNA encoding a gene for a growth factor called brain-derived neurotrophic factor (BDNF). While inserting a cochlear implant into the animals, the team injected the cochlea with a solution of BDNF DNA, then used electrical pulses from the device to create pores in the cells lining the cochlea and coax the DNA to enter the cells. The loops also included a gene for green fluorescent protein so that the scientists could see if the inserted DNA was taken up by the cells and translated into protein.

In the next few days, the cells began pumping out BDNF, which, in turn, spurred the growth of long, spiky neurons toward the electrodes. Two weeks after the treatment, the researchers tested how sensitive the animals’ brains were to sounds of various frequencies. The results were closer to those for normal animals and much better than those seen in animals that had only a cochlear implant.

“We’ve closed the neural gap,” Housley says. Although it's hard to precisely measure sound perception in guinea pigs, if applied in humans, "we're hoping that tonal colors and richness will be improved,” says Housley, whose team’s report appears today in Science Translational Medicine.

One caveat is that the improved hearing didn't last long—the cells stopped producing BDNF after about 6 weeks and the new nerves began to die. The DNA loops will have to be modified to work longer in cells, Housley says. Another potential problem is that it’s not known how long the cells that received the DNA last before they die and their BDNF-making ability is lost. Housley thinks these issues can be addressed, however, and he hopes to start a small clinical trial to test the procedure in people within 2 years.

"The idea [of using BDNF] has been around. But this is the first study to put this idea together with cochlear implants," says neuroscientist Jeffrey Holt of Boston Children's Hospital and Harvard Medical School. The technique is “ingenious,” says hearing researcher Yehoash Raphael of the University of Michigan, Ann Arbor, whose group has used a virus to insert the gene for BNDF into cochlear cells. Housley hopes other implanted devices could also deliver gene therapy, such as small electrical devices sometimes inserted into the brains of patients with Parkinson's disease to relieve their symptoms.

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