Pushing the Frontiers of Biomedical Engineering to Defeat Atherosclerosis Abdul Barakat

Research-wise, the AXA Chair has followed three major areas of focus, one fundamental in nature, the other two applied. What were the major findings?  

The first area of investigation where we have achieved success concerns vascular cells and how they respond to mechanical forces. The emerging field of mechanobiology stands at the interface of biology, engineering, and physics. It focuses on the idea that our bodies are  impacted by the mechanical environment in which we live. Using this approach, we were able to identify the involvement of a specific class of proteins, nesprins, in how mechanical stimuli are transmitted from the surface of endothelial cells to their nucleus (endothelial cells form the barrier between blood vessels and tissues and control the flow of substances and fluid that travels between the two). There was a gap in our understanding of why and how changes in blood flow impacted the subnuclear structures of these cells, a process known to be involved in the development of atherosclerosis. Having identified this protein as playing a fundamental role could lead to new avenues in treatment. Our second major research achievement is the development of artificial arteries. They are the same size as human arteries, they display the same flow, the same characteristics, and are very useful to test new medical devices and drugs. They are perfect for monitoring how interactions occur and how the cells react. Typically, medical researchers have to work with tubes, then run tests on animals, and eventually move on to human trials. We felt there was a need for another tool in between tubes and laboratory animals, to not only lower costs but also to address the ethical considerations associated with the use of animals in scientific research. This new platform has generated a lot of interest from companies making stents or blood pumps and even from more fundamental research groups studying blood clots. I should also add that we have recently developed a microvascular version of this artificial artery. Finally, the third finding I wanted to mention concerns the design of stents (metallic or polymeric wire-mesh structures that are inserted into a vessel to keep the passageway open). Using a biomechanical approach, we showed that the shape of stents, by disrupting the blood flow, affects the vascular healing process, as well as drug effectiveness. Based on engineering principles, we demonstrated that, compared to the traditional criss-cross design, a spiral stent design would lower these risks.  

An important aspect of the AXA Chair concerns technology transfer activities. Can you tell us more about the Sensome start-up, formerly Instent, and the connected stroke guidewire you helped develop?  

Out of the 7 million stents that are implanted in people’s arteries every year, ~10% or ~700 000 lead to complications. This observation led us, with a former student of mine, Franz Boszak, to the idea of connected stents, devices capable of detecting these complications and sending warning to the outside world. Together, we started the start-up Instent in 2014. We received a lot of investment at first, which allowed us to develop the stent and the sensors. However, because of the expected high cost of clinical trials, the project is currently on pause. This set-back led us to rethink our strategy, rename the company Sensome, and to converge on another highly promising application for our research: a smart guidewire to help in the timely treatment of strokes. The idea was simple: to use the same sensors as the ones developed for Instent, but this time to identify the type of blood clot blocking an artery in the event of a stroke. Did you know that only a third of stroke patients fully recover, another third die, and the rest suffer long-term disability, mostly due to the time it takes to identify the type of clot blocking the brain, which will require a different treatment approach. Our device, by considerably reducing the time it usually takes to determine the composition of the clot, can improve life and health outcomes. We are currently conducting animal trials and should be moving on to human trials at the end of the year 2020, for commercialization by early 2022.   

Since you arrived at École Polytechnique, you have committed to launching of a BioMedical Biomedical Engineering (BME) program for students. How far are you in this process? 

When I moved to France in 2010, I saw that a lot of the Polytechnique students were interested in biology and medicine, and I felt this was the best place to start a BME program in France, having observed its success in the US. I began by starting a new course, in 2010, and then another one in 2013. In 2015, we launched a master’s program. And now, at the end of 2020, we are launching an even broader 5-year program, integrating a master’s program and a PhD. In parallel, I am also involved in the creation of an Interdisciplinary Center for Bioengineering and Mathematical Life Sciences with IP Paris, a group of engineering schools..  

Any link between your research and COVID19? 

I have not worked on COVID-19 yet, but I am seriously thinking about it. Patients with the disease develop blood clot complications. Endothelial cells, and how they react to mechanical factors, must be playing a part in how the virus enters our system. It is something we at the laboratory have been really interested in, and we think we can shed some light on the mechanisms at play.  

After 10 years in France, have you noticed a shift in how researchers and medical doctors perceive multidisciplinary research such as BME?  

At the level of biologists, there is definitely more openness. Basic biology journals, like Journal of Cell biology, are now dedicating whole issues to mechanics. It has become one of the hot topics. It is also true for medical doctors. I have seen a difference in how open they are to working with physicists and engineers. Biomedical engineering, as an organized academic discipline, on the other hand, is still lacking in France, but this is where our program can change things 

From a personal perspective, what achievement are you the proudest of?  

The people that I have met and worked with, the graduate students and postdocs, in particular. They are our legacy. The human element of our job is the most important thing. Everything we do is about people. When you head such a program, you are entrusted with the future of the students you take in. They need to leave with as much as possible for the future, so that one day they can surpass us.  

What role has AXA played in the success of the project?  

The AXA Chair has been very critical to our research on atherosclerosis, providing us with resources that have been extremely useful. The AXA Chair program has also helped attract excellent students. They knew when they applied here, they were coming to a well-funded lab. It allowed them the flexibility and freedom that they would have had difficulty finding elsewhere. For that I am most grateful. The work that the AXA Research Fund is doing is essential.  

What is next? Are you heading in any new research direction? 

 Everything we have done until now revolves around cardiovascular diseases, but we are now embarking on another huge healthcare issue: Alzheimer’s disease (AD). Two of our PhD students are going in this direction. Up until now, we have mainly blamed AD on the proteins that form lesions in the brain. Over the past years, there have been a lot of efforts aimed at developing drugs to address this protein problem, but the truth is, they haven’t improved patient outcome. However, motivated by observations, a new vascular and mechanical hypothesis are emerging. It turns out that AD patients have reduced cerebral blood flow and mechanically softer brains. We think that our expertise can help shed light on the mechanical factors involved in neurodegenerative diseases including AD.  

 (1)  https://www.who.int/health-topics/cardiovascular-diseases/#tab=tab_1

November 2020