RegenVOX: phase I/II clinical trial of stem cell based tissue engineered laryngeal implants

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The larynx protects the airway during swallowing, regulates breathing, and permits voice: all fundamental human functions. Over 2000 UK patients lose laryngeal function due to trauma or cancer annually and need to spend a lot of time at or in hospitals. 1300 NHS patients a year have their larynx removed entirely. Conventional treatments for these patients leave many with substantial problems talking, swallowing and breathing. For example, the use of combined chemotherapy and radiotherapy for laryngeal cancer results in hoarseness and painful swallowing and can even render the larynx completely disabled. However, if we could accurately replace the normal contours and structure of the larynx, for example by using a living tissue-engineered replacement, the quality of life (and in some cases survival) of these patients would be transformed. In this project we build on some well-publicised successes in replacing the windpipes of adults and children to deliver a laryngeal reconstruction product made from the patient's own stem cells and a laryngeal scaffold prepared, with appropriate permissions, from transplant donors. Our goal is thereby to produce a safe, effective and reasonably therapy suitable for routine NHS use, resulting in improved quality of life for patients and carers. The product will be a partial laryngeal replacement construct, composed of a a human donor scaffold from which all donor cells have been chemically stripped. This means that the implant will not get rejected, like normal transplants, and so patients do not need immunosuppressant medication, with all the side effects that would entail. Based on extensive laboratory work, we are able to turn the patient's stem cells into cartilage-producing cells to give natural strength to the product, and also produce a replacement mucous membrane to line the inside, just like a normal larynx. Similar technology worked well for our adult and child windpipe recipients treated for life-saving reasons. To perform this work, we need a further years' preparation for a clinical trial, which will then follow ten implanted patients for two years in order to demonstrate to the regulatory authorities that the product is both safe and effective. This will, in turn, allow us to apply to use the technology routinely in the NHS and to market it to bring in much needed funds to our hospitals. Since this is the first stem-cell based organ replacement to enter clinical trials to our knowledge, this project has far-reaching 'path-finding' implications for other related organ replacements such as those for oesophagus and lung. Even more value will be obtained from this work by developing ways of studying cells and tissues in man in trials like this so that we can learn as much about the underlying science of stem cells and tissue repair as possible. Finally, we will study the detailed economics of moving treatments like this into routine healthcare, and determine the most cost-effective ways this can be managed, as well as making sure that any new inventions bring in as much finance as possible to the UK.