Background
Dental caries remains a major clinical problem and although current treatments are effective, they are “temporary repairs” rather than complete structural and functional regeneration of dentine. Despite many years of research and development into dental materials, the basic principles on which tooth restorations are based have changed little and still involve the use of inorganic filling materials to repair cavities.
Dentine is a living tissue and a source of important biological factors. If tooth cavities could be treated by stimuli that promote the formation of new dentine (tertiary dentine), then tooth integrity, structure and function can be restored. Maintaining tooth vitality is a major aim of modern dentistry, reducing the numbers of teeth that will lose structural integrity and possibly require extraction. King’s ReDent seeks to deliver on this aim of restoring and maintaining tooth vitality.
Technology
Activation of Wnt/β-catenin signalling via glycogen synthase kinase 3 (GSK-3) inhibition has been found to be pivotal for tooth repair. Prof Paul Sharpe at King’s College London’s Dental Institute has identified small molecule inhibitors of GSK-3 with the ability to repair large lesions in dentine in exposed pulp injury. A single local application of drug candidates via a collagen sponge has been shown in in vivo animal models, with similar size cavities as in humans, to promote repair through production of regenerative dentine. Thus, they may be beneficially useful in the treatment of conditions such as dental caries or dental trauma, to restore tooth vitality through a natural process leading to more effective and long-lasting repair.
Benefits
- Since treatment is applied directly into the tooth, product has a low cost of goods and potentially high margins.
- Regenerative dentine formed is compositionally and functionally identical to normal dentine.
- Local delivery ensures that there is minimal risk of systemic effects at doses utilized. This has been confirmed in ex vivo cell toxicity testing.
Figure 1: ReDent method for activating Wnt signaling in teeth using small molecule drugs
Status
King’s has collaborated with a pharma company to identify a novel GSK-3 inhibitor with supporting pre-clinical data package. MHRA has approved King’s regulatory strategy for GLP toxicology studies, which were designed with an industry-experienced toxicology consultant, who reviewed the existing data for the proposed GSK-3 inhibitor. Professor Paul Sharpe, in collaboration with the dentists in King’s Dental Institute, has also designed a randomised, single-blind, comparator controlled single ascending dose study to assess safety, tolerability and efficacy of ReDent in adult dental caries patients. The team has taken onboard MHRA advice on the proposed trial design.
Opportunity
Patent application: WO2018/073599 (priority date 21 Oct 2016) pending in Australia, Canada, China, Europe and USA.
King’s is now seeking a commercial partner to further develop and take to market the ReDent technology. A licence to the technology and know-how would be available to either an existing company looking to develop ReDent as part of its wider product offering or to a spin-out company.
Further information