Source European Commission

Atherosclerosis is a common, potentially serious condition caused by a build-up of fatty material in the lining of the artery walls. It can lead to coronary artery disease, stroke or kidney problems, and existing treatments tend to be only short-term fixes.

In response to this public health challenge, EU-funded project THE GRAIL developed a new therapeutic strategy using a soft, compliant and intelligent ‘scaffold’ made of bioactive material to trigger the regeneration of diseased areas of blood vessels. This novel medical device could soon undergo the first clinical trials in humans.

The scaffold is made of biomimetic protein – which mimics existing proteins in the body – and is known as a synthesised intimal layer. The material is bio-resorbable, meaning it dissolves into the body once healthy arterial tissue has been restored. It should provide a more effective and longer-lasting solution than the therapeutic options currently available to atherosclerosis patients.

‘As the primary cause of cardiovascular disease, atherosclerosis has been the focus of considerable research leading to rather effective treatments. But these treatments have a major shortcoming: they are mostly short-term solutions, failing to restore vessel integrity in the long term,’ says project coordinator Davide De Lucrezia of Explora Biotech in Italy.

Effective, long-term treatment

Currently, patients diagnosed with atherosclerosis are typically treated with one of two methods: bypass surgery, in which blood flow is redirected to divert it around the diseased artery; or angioplasty, in which a balloon catheter is inserted and inflated to enlarge the artery walls.

However, many patients have to return to hospital within a few years as scarring from the surgery, recurring plaque build-up and other complications cause the treated blood vessels to start narrowing again.

The treatment developed by THE GRAIL researchers overcomes these issues. Instead of bypassing or artificially inflating diseased arteries, the team’s solution involved using the thin tube of a catheter, a minimally invasive technique, to insert the synthesised intimal layer into the diseased blood vessel.

Made of biopolymers based on elastine-like proteins, the soft scaffold includes bioactive molecules that are capable of recruiting the patient’s own endothelial cells. These cells, which line the interior surface of blood vessels, support regeneration from within the diseased and stiffened area of the artery.

A dedicated spin-off

‘We demonstrated the scaffold’s full biocompatibility in vitro and safety in vivo, and preliminary results on efficacy are extremely encouraging,’ De Lucrezia says. ‘Thanks to five years of EU support, we were able to progress THE GRAIL project from a simple sketch on a paper to a working prototype, paving the way for the commercial exploitation of the results.’

Three SME partners in THE GRAIL have set up a dedicated spin-off company that owns the intellectual property generated in the project and will engage with larger companies capable of supporting sales. The consortium has also sought to exploit by-products of the research, for instance, testing a new technique for peripheral vascular bypass surgery.

Meanwhile, expertise gained in the project has allowed Explora to offer advanced in-vivo models for safety and efficacy testing of advanced medical devices, making the company one of the leading SMEs in Europe in the field of advanced therapy medicinal product testing.

The project partners are negotiating investment from venture capital firms to develop the technology, potentially leading to the first clinical trials in human patients. If successful, THE GRAIL’s synthesised intimal layer could be used in surgery within a few years, addressing a critical need for effective, long-term treatment for atherosclerosis patients.