Gene editing prevents inherited deafness in mice

Thursday December 21 2017

"Breakthrough for genetic hearing loss as gene editing prevents deafness in mice," reports The Guardian after researchers used a technique to "snip" away a gene mutation that leads to progressive deafness.

While many people assume hearing loss is something mainly associated with ageing, many cases are in fact hereditary.

It's estimated there are more than 400 forms of genetic hearing loss, many of which are progressive (they get worse over time).

The mice in the study were bred with a genetic mutation of the TMC1 gene, which causes tiny hair cells in the inner ear to die off and stop growing. As the hair cells die off, hearing becomes progressively worse.

The scientists then disabled the gene mutation by injecting a mixture of a protein and a type of genetic material called RNA into the ears of newborn mice.

They found mice that had the treatment to disable the gene mutation continued to have healthy inner ear hair cells, and could hear better than untreated mice.

This is interesting news – there's currently no treatment that can tackle the underlying causes of genetic hearing loss.

But the standard warning applies: what works in mice may not work in humans.

Where did the story come from?

The researchers who carried out the study were from Harvard University, Harvard Medical School and Tufts University in the US, and Huazhong University of Science and Technology and Shanghai Jiaotong University School of Medicine in China.

The study was funded by grants from a range of organisations, including the US National Institutes of Health and the Defence Advanced Research Projects Agency.

It was published in the peer-reviewed journal Nature.

The Mail Online reported the treatment "reversed deafness in mice" and was a "dramatic step towards a cure for children who are born deaf". This is inaccurate.

The treatment prevented mice becoming deaf, so any potential human treatment would only be useful for children born with the ability to hear but have a genetic condition that leads to progressive hearing loss.

The Guardian, The Times and The Daily Telegraph carried more balanced and accurate reports of the study.

What kind of research was this?

Scientists carried out a series of experiments in the laboratory, firstly on cells grown in the lab and then on mice.

Animal experiments are useful ways to develop new technologies and treatments before they're at a stage where they can be safely tested on humans.

But successful animal experiments don't always lead to successful treatments for humans.

What did the research involve?

Researchers carried out a series of experiments, beginning with connective tissue cells from mice (fibroblasts). They wanted to test whether the technology they'd developed could attach itself to the correct part of mouse DNA.

They used a gene-editing technology called Cas-9 RNA (nicknamed CRISPR) encased in a protein complex, which targeted a specific mutation of the TMC1 gene.

CRISPR essentially acts like a friendly infection. It can cause changes at cell levels, but these changes are beneficial, not harmful.

Once the researchers found the best gene-editing complex to use, they injected it into the inner ears of newborn mice with the TMC1 genetic mutation.

The mutation meant the mice would normally lose hair cells from the inner ear and then lose their hearing over the first 4 to 8 weeks of life.

Some mice had both ears injected, while others only had 1 ear injected, to allow for comparisons.

To test the effect of the gene editing, the scientists did a series of experiments.

They:

  • checked the brainstem's (the core of the brain) responses to sounds using electrodes that detect nerve signals through the skin
  • examined the inner ear for hair cells 8 weeks after treatment
  • checked whether mice showed a "startle response" to sudden noises at different noise thresholds

They also injected mice without the TMC1 mutation to see if the complex had any effect on their hearing.

What were the basic results?

The ears injected with gene editing complex:

  • produced brain responses to sounds at a much lower level than untreated ears – untreated ears produced brain responses to sounds only above 70 to 90 decibels (dB) at 4 weeks of age, while treated ears produced responses to sounds 15dB lower on average (70dB is roughly equivalent to the noise level of busy traffic)
  • had far more remaining inner ear hairs compared with untreated ears 8 weeks after treatment

Mice that hadn't been treated in either ear didn't respond to sounds at 120dB (about the noise of a plane taking off) at 8 weeks of age. In contrast, treated mice showed a startle response to sounds at 110dB and 120dB.

The gene complex seemed to have little or no effect when injected into mice without a mutated TMC1 gene.

How did the researchers interpret the results?

The researchers said they'd shown their gene-editing technique worked in mice with a mutated TMC1 gene and affected the development of hearing loss.

"The genome editing strategy developed here may inform the future development of a DNA-free, virus-free, one-time treatment for certain genetic hearing loss disorders," they said.

Conclusion

This study demonstrates how gene-editing technology is improving to the extent it can be used in animals to target specific gene mutations and affect their resulting conditions.

But a technique that works in the short term in mice may not work – or even be safe – in humans.

Animal studies have limitations when testing treatments that might one day be applied to humans. This is partly because of the obvious differences between species, but also because of the timescale of the studies.

This study took place over a short period of time (8 weeks), so we don't know what the long-term outcome of the treatment might have been on the mice's hearing or any other aspects of their health.

The treatment was able to prevent hearing loss in mice because most animals have 2 copies of the TMC1 gene (1 from each parent), so disrupting the faulty gene means the normal gene can do its job.

That allowed the hair cells in the inner ear to grow so hearing levels were preserved in the treated mice.

In the UK, about 1 in 1,600 children have hearing loss because they inherit a mutated gene. Some of these children will have a dominantly inherited gene, with 1 normal gene, as in this study.

We don't yet know how many children develop hearing loss that could potentially be treated by editing this specific gene.

While this study might offer hope that some types of genetically inherited hearing loss could one day be treated using gene editing, there's a long way to go before the technology would be ready to use on newborn babies.

Analysis by Bazian
Edited by NHS Website