Breakthrough Alert: Researchers Edit Faulty Gene to Disrupt Hearing Loss
Hearing requires the conversion of acoustic energy into electrical signals. Sound waves travel through the ear and wash over the hair cells of the inner ear, which bend under pressure and send an electrical impulse up the auditory nerve to the brain.
Nearly half of all cases of deafness are due in some part to genetic factors, and many of those gene mutations affect the functioning of hair cells. The most common cause of genetic hearing loss, accounting for 20 percent of cases, is a recessive connexin 26 mutation on the GBJ2 gene.
For people with the condition, hearing loss begins in childhood and deafness ensues within 10 to 15 years.
A recessive disease mutation requires a copy of the mutation from both parents. By contrast, one parent can pass along a dominant disease mutation like the one in the TMC1 gene, cause of 4 to 8 percent of cases of genetic hearing loss. TMC1 creates a defect in a protein that helps convert sounds into electrical signals, while the healthy copy of the gene is simply ignored.
Now, in a ground breaking study, researchers have been able to prevent deafness in mice using gene editing
. “We’re hopeful that our results will help guide the development of similar strategies,” says David Liu, a genetic engineer at Broad Institute, the Massachusetts Institute of Technology and Harvard University.The research relies the CRISPR–Cas9 editing system to knock out a mutant form of the gene Tmc1. In doing so, it lays out a potential pathway for treating other genetic causes of hearing loss.
Liu performed his experiments on a type of mouse known as a Beethoven mouse. These mice carry a defect that causes them to lose their hearing starting early in life. It’s probably not what caused the famous German composer Ludwig von Beethoven’s deafness. Still, the same defect does cause deafness in some families.
The researchers then injected the gene editing tool inside the ears of the live mice; the molecular scissors were able to precisely cut the disease-causing copy of the gene without disrupting the healthy copy. Eight weeks after the injection, hair cells in treated ears resembled those in healthy animals – densely packed and tufted with hairlike bundles. The hair cells of untreated mice, in contrast, looked damaged and sparse.
Then the researchers conducted a hearing test on the mice by placing electrodes on their heads and monitoring the activity of brain regions involved in hearing. Researchers needed more sound to spark brain activity in untreated mice compared with treated mice, the team found.
On average, after four weeks, treated ears could hear sounds about 15 decibels lower than untreated ears. “That’s roughly the difference between a quiet conversation and a garbage disposal,” Liu said.
Because CRISPR-Cas9 can be guided to any gene, rewriting DNA with gene editing is akin to rewriting software. Other forms of deafness attributable to an errant copy of a single gene might also be ameliorated using the same technique. Altogether such cases amount to about 20 percent of genetic deafness.
Lustig, who works with patients with hearing loss every day, says Liu’s results are “significant” and offer hope for gene editing as a treatment. “It’s not around the corner,” he says, “but we’re on the pathway.”
Moving forward, delivery methods, improved efficacy, and an investigation into potential side effects are top priorities. These steps are crucial if we’re to find out whether the procedure could give medical professionals a way to restore their patients’ hearing. “There’s still quite a bit of work to do before this approach might be used in humans,” Liu said.
