The future for cochlear implants
30 January 2003
Cochlear implants have a very bright future. There has been a great deal of progress over the past few decades but there is substantial room for further development, as Professor Matthew Holley explains.
In 1995 Professor Stuart Rosen discussed the potential for future developments in an introductory booklet to cochlear implants published by The National Association of Deafened People. He accurately predicted significant advances in electrode design and in signal processing.
However, while making room for the unpredictable he mischievously suggested that advances in tissue regeneration might render the implants obsolete. In reality it is much more likely that new developments in tissue regeneration will serve to enhance the biological interface with the implant, improving its performance and making it available to a wider range of people.
Over the past 15 years there have been many new, scientifically exciting insights into the way the ear develops. Scientists around the world are continually searching for genes and other molecules that might stimulate the growth of new sensory cells or nerves. Each discovery excites those who do the research and can open opportunities for future therapeutic approaches but the road to a clinical application is long and unpredictable. In the late 1980s the discovery that birds and reptiles could replace lost hair cells, the sensory cells that detect sound, raised hopes that it might be possible to stimulate regeneration of sensory cells within the human ear. Many scientists do not reject this idea but they believe that it is unlikely to yield practical results in the foreseeable future. In contrast, a range of experimental evidence shows that it should be possible to protect or even stimulate regrowth of the auditory nerve supply.
The cochlear implant electrode bypasses the sensory cells and stimulates the auditory nerve directly. Ideally, the patient should have a full set of auditory nerve cells with processes (fibres) that extend through the bony structures of the cochlea to the place where the hair cells used to be. Unfortunately, loss of hair cells invariably leads to regression of nerve processes and loss of nerve cells. Furthermore, bone is a good electrical insulator so it is not easy to provide precise, low level stimulation to cells that have retreated within it. Implants are not normally considered until hearing loss is severe and the nerves have had a chance to die back through lack of use.
The nerve supply normally depends upon the activity of the hair cells. Hair cells keep the nerve processes interested by exciting them with electrical signals and by secreting chemicals called growth factors. Electrical activity helps to maintain nerves that are already connected but growth factors can actually encourage the re-growth of nerve processes and possibly even lead to the formation of new nerve cells. The effects of electrical stimulation work at least in part by causing release of growth factors within the nerves.
Can growth factors be delivered in conjunction with the cochlear implant to help restore the nerve supply? Animal experiments suggest that this should be possible but clinical trials have not yet taken place. Several problems must be solved before clinical trials can be attempted, including the method of delivering growth factors to the ear over a long time scale and the limitation of side effects. The latter is particularly important because growth factors are not specific to hair cells and they will potentially stimulate many other cell types.
There are numerous methods of delivering growth factors, including direct infusion, gene therapy designed to encourage remaining cochlear cells to make their own, and transplantation of cells that might mimic the chemical effects of normal hair cells within the cochlea. All approaches are being pursued but direct delivery via a miniature pump or catheter is the most advanced method at this stage. An optimistic view might be to aim for clinical trials in 3-5 years but this depends upon positive results from the animal models. Furthermore, exciting nerve growth is one thing but it must also lead to a measurably better performance of the cochlear implant.
Predicting the rate of scientific progress is extremely difficult. Most of the time progress is frustratingly slow, as exemplified by the clinical application of growth factors and gene therapy in many different areas of medicine. Over the past few years, however, there has been an explosion of interest in the therapeutic application of stem cells. Stem cells are young cells that can reproduce themselves and also give rise to various mature cell types. They occur naturally in some adult tissues such as the skin where they continually replace lost skin cells, but they are not readily found in other tissues, including the brain and inner ear sensory epithelia. There is now a huge interest and activity in exploring the potential of various types of stem cell to repair tissues that do not normally regenerate. New ideas and results are pouring from laboratories across the world and governments are busy trying to prepare legislation that will allow measured, beneficial progress.
How might this technology apply to the ear? Cell transplantation to the brain has resulted in some extremely successful results in animal models and clinical trials for a variety of different approaches are now taking place. Embryonic 'ear stem cells' or 'ear cell progenitors' from embryonic mice have been established using a genetic modification similar to one that has proved successful with brain cells. However, transplantation studies have not been done in animals and there have been no published attempts to establish appropriate human cells. The ear is one of the most complex and therapeutically challenging organs in the body but recent progress with the apparently intransigent central nervous system has taught scientists not to be too pessimistic. The prospect of replacing auditory nerve cells is worth a try but cannot be viewed as a realistic treatment in the foreseeable future.
Apart from cell transplantation, there are other reasons for making cells from the developing ear. The inner ear is a very small, complex organ, built before birth and protected by several layers of bone. The cells provide tools for exploring the genetic mechanisms that drive the development of different cell types. They also provide a model for screening potential new drugs. This is only one of numerous avenues of research and we can expect considerable progress over the next 5-10 years, during which time we should discover a great deal more about the potential of the cochlear implant.
