School of Medicine

Current approaches to improving glycaemic control in type 1 diabetes are centered on increasingly complex insulin delivery systems. However, less than 30% of patients can achieve target levels of glucose control with this approach even in a clinical trial setting and many patients are either unable or unwilling to make the personal commitment required. By contrast, preservation of even small amounts of endogenous insulin production, has been shown to improve glycaemic control, reduce hypoglycaemia, improve quality of life and reduce long-term complications. Importantly, glycemic control in the presence of endogenous beta cell function is not demanding and hence would be effective across the full spectrum of individuals. Antigen specific immunotherapy (ASI) is the preferred approach to beta cell preservation since this avoids the risks of immunosuppression. Attempts at ASI to date although successful in preclinical models have had limited efficacy in humans. There is therefore an urgent need for the development of novel approaches to deliver effective ASI.

The Enhanced Epidermal – Antigen Specific Immunotherapy (EE-ASI) system represents an innovative approach to ASI created by combining technologies brought by our academic and 2 SME partners. A beta cell target T cell epitope (proinsulin C19-A3) will be combined with the tolerogenic cytokine IL-10 and targeted to antigen presenting cells via gold nanoparticles and delivery into the very superficial layers of the skin using microneedles. Validation of manufactue, in vitro and in vivo preclinical efficacy will be demonstrated followed by a phase 1 clinical trial to confirm safety in humans.

It is anticipated that the EE-ASI system will be less costly, more effective and more acceptable to patients in improving glycaemic control than exogenous insulin replacement. Intellectual property, regulatory and ethical issues will be carefully addressed in order to maximise exploitation of this integrated system for the benefit of the SMEs.