Smart Insulin

On August 17, Novo Nordisk announced the acquisition of a startup company called Ziylo. The sale, could be worth as much as £620 million, depending on commercial targets being met over the next decade. Ziylo has pioneered work that could lead to the development of a type of insulin which responds to changing blood glucose levels with an “on/off switch”, which could reduce the likelihood that diabetics will crash into hypoglycemia.    These glucose responsive insulins (GRI) are often referred to as smart insulins.   The lower or higher blood sugar levels are, less or more insulin is released or made active, respectively.  The insulin is designed to be effective for many hours and keeps blood glucose levels normal throughout the day.

Smart insulin has been the goal of a number of companies and research units for some years. Some argue it would afford the ultimate solution for insulin administration, working when needed and switching off when not needed – avoiding the need for cannulae, catheters, pumps, sensors, batteries, blocked lines and being completely unobtrusive.  All three Big Insulin makers (Novo Nordisk, Sanofi Aventis and Lilly) have significant investments in the game, and the JDRF too has made a significant investment in this area.

However there are two other ways in which Glucose Responsive insulins have been developed. The first is using continuous glucose monitors and insulin pumps linked in a closed loop by hierarchical control algorithms.

The second is with the use of polymer-based glucose responsive insulins where the insulin is encapsulated within a glucose sensitive polymeric matrix.  Polymer and Matrix-Based GRI systems rely on sequestration of native or derivatized insulin molecules within a matrix suitable for subcutaneous injection. The matrix is designed to sense ambient glucose concentrations and release a proportional amount of insulin for systemic absorption. The polymeric glucose sensitive matrix can be encapsulated in large implants, in transdermal patches or in micro or nanoparticles.

Two of the best known of these systems are from North Carolina, USA and Birmingham, UK.  Dr. Zhen Gu, a biomedical engineer and professor at North Carolina State/UNC, has developed a microneedle patch design for delivering glucose responsive insulin. His research has also evolved more recently into testing this patch design tech covered in live beta cells, which could deliver the new smart insulin in much the same way. Because these beta cells are kept within a patch on the outside of the body, there is no danger of them being rejected by the immune systems of people with type 1 diabetes.

In the UK, progress is being made on a smart insulin capsule that rests inside the body and releases insulin when blood sugars are too high.  The University of Birmingham’s capsule contains molecules that bind to glucose, and when glucose levels are high, the capsule melts away, releasing the insulin.

All smart insulin projects are at a very early stage and, in some cases, the drug is still being tested in animal studies but there is considerable promise that this approach will lead to a substantial improvement in glucose management in insulin dependent individuals.