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The Regeneration Game

When the hair cells in our ears are lost, they’re gone for good. Can scientists regenerate them – and restore hearing? Carina Santos from our Biomedical Research team tells us more.

The ear is an extraordinary organ. It’s super-sensitive to sound, allowing us to hear the gentlest whisper or the chirp of a bird in noisy traffic. But it has one distinct drawback. While the eye and nose have millions of receptors, the ear relies on 15,000 hair cells to detect and turn sound into electric signals, the only ‘language’ our brain understands. What’s worse, if we lose any of those 15,000 hair cells, they won’t regenerate. The result is sensorineural hearing loss.

Microscope image of hair cells in the inner ear

The ear has three specific parts:

  • the external ear that captures the sound around us
  • the middle ear that amplifies the sound
  • the inner ear that transforms sounds into electric signals. This is done by the hair cells (they have tiny projections that look like hair) that are extraordinarily sensitive to sound. Unfortunately, they’re easily damaged by loud noise, certain drugs, and by the ageing process.

Watch the birdy

We can’t regenerate our hair cells – but what about our feathered friends? Birds’ hair cells can be damaged again and again, and they’ll regenerate within weeks. That’s why scientists around the world are doing their utmost to understand how this regeneration takes place (and, as we’ve told you before, they’re studying fish as well as birds).

Armed with this knowledge, they’ll be able to develop therapies to trigger the regeneration of hair cells in humans. Exciting progress has already been made and some regenerative therapies are being tested on people. In birds, once the hair cells are destroyed, the supporting cells (cells surrounding the hair cells which help them to function) start dividing and give rise to new hair cells, which results in the regeneration of the bird’s hearing. Unfortunately, this doesn’t happen in people – so scientists are developing treatments to give a little push to the supporting cells in the human ear to make them behave like the ones in birds.

Unlocking potential

How can ear regeneration, observed in birds and fish, be unlocked in us? Some of the biggest pharmaceutical companies, such as GenVec, and Novartis, are now testing whether this breakthrough therapy is safe. The CGF166 consists of a gene therapy that will give supporting cells the ‘small push’ they need to induce them to produce new hair cells. Gene therapy is a way to introduce genes into cells. In this case, researchers are introducing a gene called Atoh1 into the ear. This activates the cellular pathway in supporting cells that will trigger their conversion into hair cells. It’s being tested in people with profound to severe hearing loss.

At the same time, a new clinical trial is underway in the UK. Dutch biotech company, Audion Therapeutics, in association with pharmaceutical giants, Eli Lilly, is testing a small-molecule drug called a Gamma Secretase Inhibitor (GSI). This drug inhibits, or blocks, a specific cellular pathway, and induces the formation of new hair cells from supporting cells. When the gene and drug therapies mentioned earlier were tested on animals, the results were encouraging: supporting cells were converted into new hair cells – and the animals’ hearing improved.

Stem cell therapies

Equally exciting in terms of curing hearing loss, but at a slightly earlier stage of development, are the stem cell therapies. Stem cells are cells that have the capacity to produce any other cell type in our body. With our funding, Dr Marcelo Rivolta, at the University of Sheffield, has succeeded in producing hair cells, as well as Spiral Ganglia Neurons (SGNs), from embryonic stem cells. SGNs connect the hair cells to the brain. Like the hair cells themselves, they can degenerate and lead to hearing loss. Dr Rivolta and his team were able to produce SGNs from stem cells and transplant them to deaf gerbils. The initial results were very promising – the gerbils recovered 46% of their hearing.

An ever-growing number of researchers are choosing to work in this field – and more pharmaceutical companies are investing time and money in developing these therapies. This March, we’re holding a major research summit, bringing together pharmaceutical companies, scientists and clinicians. They’ll share progress, discuss the challenges they face – and agree on how to speed up the development of treatments. Watch this space!

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