Hearing Loss Prevented With CRISPR Gene Therapy in Extraordinary Advancement

Updated | A genetic editing tool known as CRISPR-Cas9 has been shown to prevent hearing loss caused by a genetic mutation. A new paper published in Nature on Wednesday proves that gene therapies work to reverse genetic hearing loss in mice and may be a decade or more away from being used in human patients, although a key question that cannot be ignored is what the Deaf community may think of these potential treatments.

Regardless, the results of Wednesday's paper, released one day after the FDA approved the first-ever gene therapy intended to treat a specific mutation, are compelling. "I think it's pretty exciting. I think it's doing real gene therapy with CRISPR editing in the mouse but also in a context that you can see the future for doing the same type of thing in humans," Peter Barr-Gillespie told Newsweek. (Barr-Gillespie, a hearing researcher at Oregon Health & Science University, was not involved in the research.)

Hearing loss is the most common sensory issue that people experience, according to a 2014 paper published in Science. Up to 300 million people may be affected, though not all of them have genetic causes for their hearing loss. These experiments were all done in mice made to have a particular genetic mutation that's also found in humans. Like the majority of genetic mutations that can cause diseases in humans, this mutation means just one DNA base pair in a copy of a gene called TMC1—is off. That's enough to render one of the channels necessary for specialized cells in the inner ear unable to function, which causes those ear cells to die off. Those cells, called hair cells, are responsible for sending signals from ears to the brain—without them, people can't hear.

"Sometime during childhood, the hearing loss becomes substantial," said David Liu, a researcher at the Broad Institute, the Howard Hughes Medical Institute and Harvard and one of the authors of the paper. That loss may start in the first ten or twenty years of a person's life and continue to get worse as they get older.

This particular mutation has a nickname: the Beethoven mutation, named after the famous German composer who progressively lost his hearing. "There's no shortage of examples of scientists naming their genes after cute cultural references," Liu said. "Although it frequently raises the question whether Beethoven was deaf because of this disease, which I don't think he was."

The particular gene-editing tool that Liu and his colleagues used, CRISPR, has received a lot of attention from the scientific community. More properly called CRISPR-Cas9, the system works by making a cut in a cell's DNA sequence, forcing it to make repairs. That cut disrupts the mutated TMC1 gene—meaning that it can no longer make the mutated, harmful version of the protein at all.

The researchers did a number of experiments to see if CRISPR would work in this case, including one that measured how a mouse's ability to hear and the health of the cells in their ears changed after the treatment. For each mouse, Liu and his colleagues treated one ear and left the other alone. Then, they tested how each mouse's responded to loud noises appeared to change and how many of the cells in the inner ear had been edited.

The technique didn't affect every single cell—between 10 and 25 percent of the cells in a mouse's inner ear may have been edited, though Liu stressed those estimates were very rough. But even that made a difference; researchers estimated that mice with treated ears would be able to hear a conversation while mice with untreated ears wouldn't be able to hear anything quieter than a running garbage disposal.

"If we could get that kind of hearing preservation to translate into humans—and that's not proven yet, because this is just a study purely done in mice—that kind of improvement, that magnitude of improvement, could increase the quality of life of those patients substantially," Liu said. (However, Liu stressed, deafness doesn't necessarily mean a lower quality of life.)

If this kind of therapy does eventually make its way into humans, it will likely stir controversy. Gene editing has already triggered some ethical concerns. Who will be able to access these kinds of treatments is one question; whether editing a fetus's genome is ethical at all is another. Treatments that affect the Deaf community—genome editing or otherwise—have additional concerns to grapple with. Deafness is more than a condition for many. It's an identity and a culture with its own language. Treatments that might undermine that identity can be controversial, like cochlear implants. These implants, used to restore the hearing of infants born Deaf, first came on the market in the 1980s.

However, Liu said, "without commenting on the cultural aspects of it, I think having the option to avoid sensory loss is helpful to people." Barr-Gillespie agreed. "I remember the Deaf community's objections to cochlear implants," he said. "And I understand where they're coming from. It's a conversation that needs to happen, to be sure. But then again, ultimately, I think the people who matter the most are the parents [of children with the condition]." (Newsweek also contacted the National Association of the Deaf for comment; none had been received by Wednesday morning.)

There will, in fact, be years to have these discussions; this therapy is still far from being available in clinics. The next step, said Zheng-Yi Chen, a hearing researcher at the Massachusetts Eye and Ear Institute and one of the authors of the paper, would be to use human stem cells as well as a larger animal model, like a pig to further test the therapy. These experiments may start early in the new year.

This article has been updated with information about the prevalence of hearing loss.