Novel Amphibian Skin Peptides for Treatment of Diabetes (U366)

Tuesday, 25 October 2016

Researchers at Ulster University are internationally known for their expertise in the discovery and development of natural product-based peptides for diabetes. Such underpinning research has led to this Proof of Concept study resulting in the preclinical development of novel analogues derived from the natural product peptide, esculentin originally isolated from the skin secretion of the Chiricahua Leopard Frog, Lithobates chiricahuensis.

Problem Being Solved

Diabetes is a metabolic disorder characterized by hyperglycemia, which results from the body’s impaired response (or resistance) to the actions of insulin. The prevention of type 2 diabetes is a pressing public health issue and its incidence and prevalence are increasing significantly globally. Estimates expect 440 million type 2 diabetic people globally by 2030.

Therapeutic peptides are one of the most attractive and emerging therapies currently being developed for diabetes due to their numerous advantages over small molecules and/or biologics which include high potency, low toxicity, high specificity, low risk of organ accumulation and drug-drug interaction.

Technology

The recently completed Proof of Concept study has led to the preclinical development of novel analogues derived from the natural product peptide, Esculentin, originally isolated from the skin secretion of the Chiricahua Leopard Frog, Lithobates chiricahuensis.

Results demonstrated that the truncated form of esculentin i.e. esculentin-2CHa-(GA30) possesses enhanced insulinotropic effects as compared to the native peptide. To further enhance the peptide’s bioactivity and metabolic stability, a series of nine synthetic analogues with various modifications were generated resulting in two lead analogues, [D-Arg7, D-Lys15,D-Lys23]-esculentin-2CHa-(GA30)] and Lys15-octanoate -Esculentin-2CHa-(GA30). Acute studies demonstrated Ulster’s lead analogues to reduce non-fasting blood glucose, improve glucose tolerance and insulin release.  Lead analogues were also evaluated in a chronic (28d), head-to-head study in high-fat-fed mice compared to exendin-4 demonstrating promising potential in improving glucose tolerance through reduction of blood glucose levels and increase in plasma insulin.

 While further studies are needed, a robust pre-clinical data package relating to stable lead peptides with insulinotropic, glucose-lowering effects presents a potential early-stage licensing opportunity.

Benefits/Applications

  • Compounds can be generated using simple synthetic methodology;
  • Analogues are short in length and have been designed to withstand degradation with lead analogues possessing increased stability as compared to native peptide;
  • Stable lead peptides have insulinotropic, glucose-lowering effects and improved glucose tolerance;
  • Comparable effects to exendin-4 on reducing HbA1c.

Opportunity/Partnership Sought

Ulster University is actively seeking a strategic partner to assist in the further development of this exciting technology, providing a route to market for the safe and effective treatment of obesity and associated type 2 diabetes.

 The University is open to a variety of models for collaboration including sponsored research, out-licensing and co-development.  In addition, the inventors of this technology are able to provide valuable know-how in order to assist with its successful commercialisation.

For more information please contact:

Dr Oonagh Lynch

Technology Commercialisation Executive

Research & Impact

Tel: +44 (0) 28 9036 6707

Mob: +44 (0) 77 6536 3191

Email:ot.lynch@ulster.ac.uk