Cambridge biotech targets potential treatment for diabetes

EPM editor Reece Armstrong examines the story behind a Cambridge-based biotech’s potential treatment for diabetes.

A Cambridge-based biotech company has developed a novel way of potentially treating a range of diseases.

ET-traps has developed a therapy targeting the Endothelin – 1 (ET-1) molecule which has significantly elevated levels in a host of different diseases including diabetes and neurodegenerative disorders, where it is largely responsible for the pathological processes in these diseases.

ET-1 is a vasoconstrictor, proinflammatory and proliferative endothelial cell-derived peptide that helps the vascular system function properly. First discovered in 1988, ET-1 was quickly identified as being an important molecule due to it being present in all humans, with its levels significantly elevated in different diseases. While there are endothelin antagonists in clinical use to block ET-1’s function, there are many side-effects such as an increased heart rate associated in doing this. More so, certain endothelin antagonists can interfere with anticoagulants, necessitating a move away from these types of therapies. 

That’s why ET-traps has developed a novel tool to bind and sequester these pathologically elevated ET-1 levels in different disease models.

The idea is that controlling the levels of ET-1 could potentially save the lives of millions of patients. 

ET-traps was founded by Dr Arjun Jain who started developing the idea when he was a Marie Curie post-doctoral researcher in Bern, Switzerland. Dr Jain took an innovative approach by sequestering ET-1 at a time when many experts thought that the idea was impossible.

The company has now completed proof of concept studies in cellular and animal models in the diabetes disease space.

As one of the most common diseases in the world diabetes now affects over 422 million people, according to the World Health Organisation. In fact, the NHS is estimated to spend around £14 billion every year on treating diabetes and its complications, making it one of the largest expenditures for the organisation.

Indicated to treat both type-1 and type-2 diabetes, ET-traps will aim to bring back the pathologically elevated levels of ET-1 and repair any damage caused to a patient’s vital organs due to complications caused by their diabetes.

In particular, what ET-traps has developed is an Fc-based fusion protein that has a very high binding affinity in the picomolar range, which the company states is higher than the endothelin receptor antagonists (ERAs) that are already in clinical use.

Results from the company’s in vivo studies demonstrating ET-traps’ efficacy in treating diabetes showed that the drug significantly reduced collagen 4α1 expression in the heart and kidney, returning it back to non-diabetic levels.

ET-traps has now filed a patent for its therapy and is working with investors on extending the patent life and applying it in other therapeutic areas.

Commenting on the drug’s use for diabetes, ET-traps founder Dr Arjun Jain said: “Currently, other than insulin, which controls glucose levels, there is no real cure for this devastating disease which often starts in childhood (in the case of type-1 diabetes). The endothelin receptor antagonists are currently not approved for use in children, as they are associated with toxicity. The ET-traps exhibited no toxicity in the proof-of-concept studies done. Therefore, we believe that this would offer a new cure that could help save millions of lives!