Stem cell 'deafness cure' (but only in gerbils)

“Deaf gerbils ‘hear again’ after stem cell cure,” BBC News has reported. “UK researchers have taken a huge step forward in treating deafness” the broadcaster added.

This news, reported in most places today, is based on a study that examined the possibility of treating a specific type of deafness known as auditory neuropathy. This is a condition where specialised nerve cells involved in hearing become damaged or die, for reasons that aren't fully understood.

In this study, the researchers experimented by replacing the damaged nerve cells with new ones grown from human stem cells. Stem cells are essentially biological “building blocks” that have the ability to transform into a wide range of specialised cells, including nerve cells.

They then injected these new cells into the inner ears of deliberately deafened gerbils, and measured their responses to sound both before and after the transplant.

The researchers found that, on average, gerbils that had had stem cell transplants showed a 46% improvement in hearing, compared with gerbils that did not receive the transplant. The improvement was not uniform as some gerbils responded better to treatment than others.

This is promising early research into the effectiveness of stem-cell-derived nerve cells in treating deafness. There are several hurdles to overcome before this technology can be applied to people with auditory neuropathy. Researchers will need to develop a technique for transplanting these cells into the human inner ear, and to study the safety and long-term effectiveness of this transplant in treating human deafness.

Where did the story come from?

The study was carried out by researchers from the University of Sheffield and Srinakharinwirot University in Bangkok, Thailand. It was funded by the UK charities Action on Hearing Loss, Deafness Research UK and the Wellcome Trust, as well as the Medical Research Council.

The study was published in the peer-reviewed journal Nature.

This research was covered quite well by the media. In particular, The Independent appropriately reported on not only the research methods and results, but also the limitations of the study. It emphasised that the purpose of the study was to test the feasibility of the technique (known as “proof of concept”), and that this was an early stage of the research.

What kind of research was this?

This was an animal study that examined the effectiveness of using stem-cell-derived auditory nerve cells to treat a specific type of deafness. This research examined two of the main structures in the ear that are responsible for transmitting sound to the brain:

• sensory hair cells
• nerve cells called spiral ganglion neurons

Damage to either of these structures can lead to hearing loss. This study focused mainly on a form of auditory neuropathy that arises due to damage to the nerve cells that carry sound from the inner ear to the brain. This type of deafness can not be alleviated by current treatments such as cochlear implants. There are other other causes of auditory neuropathy which are responsive to current treatments.

Animal studies are frequently used in the early stages of clinical research in order to test the feasibility of a new treatment. Once these proof-of-concept studies are completed, there is still significantly more research required. Additional techniques must be developed to test the treatment in people, and further studies are needed to test its safety and effectiveness.

What did the research involve?

The researchers used human embryonic stem cells to develop cells known as “otic progenitors”. The cells were then able to develop into spiral ganglion neurons (SGNs), the nerve cells found in the inner ear, which send auditory signals to the brain. The researchers induced severe hearing loss by damaging the spiral ganglion neurons of two groups of gerbils: a transplant group of 18 gerbils and a control group of eight gerbils. They then transplanted the otic progenitors into the inner ear of the transplant group, and monitored whether:

• The progenitors integrated into the inner ear structure.
• The progenitors fully developed into SGNs.
• The developed SGNs were able to send signals to the brain and improve hearing.

The researchers measured functional performance (or hearing) every one to two weeks for 10 weeks, using a technique called "auditory-evoked brainstem response" (ABR). According to the US National Institutes of Health, ABR uses electrodes to measure brain wave activity in response to sound. The researchers assessed the level of sound (measured in decibels) at which a response was seen, with brain activity at lower decibels indicating better hearing. The researchers calculated the difference in hearing within the groups throughout the experiment, and also compared the overall difference at 10 weeks between the two groups.

What were the basic results?

The researchers found that otic progenitor cells were able to integrate into the inner ear structure and to develop into nerve cells. When measuring the hearing of the gerbils, the researchers found that:

• Gerbils in the control group showed no improvement in hearing over the 10-week experiment.
• Gerbils in the transplant group demonstrated improved hearing within four weeks of the transplant.
• The transplant group had an average hearing improvement of 46% after 10 weeks, compared with the control group – one researcher was quoted on the New Scientist website as comparing this level of improvement with “going from only being able to hear a loud truck on the street to being able to hold a conversation”.
• Some of the gerbils in the transplant group experienced near complete restoration of hearing after 10 weeks. However, others experienced little to no improvement compared with the control group.

How did the researchers interpret the results?

The researchers concluded that their results “pave the way for future cell-based treatment for auditory neuropathies” and could potentially be combined with the existing cochlear implant technology to treat hearing loss in “a wider range of patients, who currently remain without viable treatment”.

Conclusion

This early animal research supports the feasibility of using human embryonic stem cells as a treatment for a certain type of deafness or hearing impairment. Before this technique can be offered to people with this type of deafness, researchers will need to address several obstacles.

First, the inner ear is very small, and transplanting the cells to the precise location required is likely to be difficult. A procedure will need to be developed and tested in order to overcome this difficulty.

Second, researchers will need to carry out a series of experiments in humans to confirm that such transplants are both a safe and effective treatment for auditory neuropathy as seen in people. Treatments that are deemed promising based on animal models can be unsafe or ineffective in humans.

Third, aside from the scientific hurdles, there is considerable ethical controversy regarding the use of stem cells, especially human embryonic stem cells, in both research and therapeutics. This is because most embryonic stem cells are derived from eggs, provided by consenting IVF donors. This technique has met with criticism from some religious groups who argue it is a similar process to abortion, in that a potential human life is not allowed to come to fruition.

Finally, it is important to remember that this technology may potentially treat a very specific type of hearing impairment: auditory neuropathy arising from damaged auditory nerve cells.

Other more common types of deafness, such as presbycusis (age-related hearing loss caused by gradual “wear and tear”), which is the most common cause of gradual hearing loss in older adults, are not targeted by this technology. So, while this transplant may one day offer a treatment for some individuals, it will not offer an overall “cure for deafness” for people as implied by some newspaper headlines.