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Associate Professor Mohit Shivdasani is an engineer-scientist by profession, with a range of notable accomplishments to his name. At this point in his career, there is nothing that gives him greater satisfaction than joining forces with colleagues from other disciplines to identify real-world clinical needs, and devise game-changing solutions.

“My main love is learning from different people,” he says. “I love talking to the clinicians and going, ‘Well, what is your problem and how can we solve it?’ I bring the engineering perspective. I think like an engineer. I don’t think like a clinician.”

For many years, Mohit has specialised in the development of devices that stimulate the nervous system, making important contributions to projects that have helped restore hearing, and more recently to a ‘bionic eye’ that has undergone testing in humans. He was curious to learn how his expertise in neurostimulation could benefit colleagues working in the field of gastroenterology, and in particular Inflammatory Bowel Disease (IBD). 

“IBD causes chronic inflammation of the gastrointestinal tract. It's very debilitating, and there's no cure for it,” he says. “Once a patient is diagnosed with IBD, they will live with IBD for the rest of their life, and the symptoms are terrible: diarrhoea, constant abdominal pain, swelling, inflammation–it could even lead to colon cancer.”

In consultation with clinical colleagues, Mohit learned that the immunosuppressants and other pharmacological interventions commonly used to treat people with IBD are not always effective, or can become less effective over time. For some patients, immunosuppressants can even increase the risk of infection, skin cancer and lymphoma. 

Additionally, clinicians shared their frustration at not being able to adjust a patient’s treatment until they were already suffering the severe consequences of an inflammatory flare up. It was this need that Mohit and his team felt they could address by developing a device that would monitor inflammation in the gut, enabling clinicians to pre-emptively adapt a patient’s treatment to reduce the impact of an impending inflammatory episode.

After some discussion, a decision was made to focus on the monitoring of cytokines.

Cytokines

“Cytokines are chemical proteins that signal inflammation in the body,” explains Mohit. “Chemical signalling is part of the body's way of communicating with the brain. Most people think it's purely the nervous system, but it's a combination of nerves and chemicals together.”

Sensors capable of measuring cytokines had been built before, but none that were designed to be implanted indefinitely in the delicate and complex environment of the gastrointestinal tract. As the ‘AutoGut’ project progressed, Mohit and his team became aware of just how impactful this new device could be. Certainly, the sensor could help a clinician track their patients’ data and tailor treatments to match–but what if it could become part of a system that also regulated therapy automatically, without the need for a clinician to intermittently intervene in their patient’s treatment.

The idea for this ‘closed-loop’ intervention was aligned to the use of bioelectronic therapy to treat the symptoms of IBD. An alternative to pharmaceutical immunosuppressants, bioelectronic therapy involves the electrical stimulation of the vagus nerve, inducing significant anti-inflammatory effects. Dr Sophie Payne, a collaborator from the Bionics Institute has already developed a vagus nerve stimulation treatment for IBD and the team decided to capitalise on this.

Controlling inflammation

“That's how the brain controls inflammation, through this vagus nerve,” says Mohit. “And it  turns out that if you tap into this ‘phone line’ of the vagus nerve, and knock, knock, knock with stimulation, you can actually suppress the inflammation.”

Mohit’s vision was that, when inflammation was high, the cytokine biosensor would command the device to stimulate the vagus nerve into action, and when it dropped, it would signal the stimulator to stop. 

“The point is, we treat it when we need to treat it, and we don't give unnecessary treatment,” he says. “There's no guessing involved. So, you not only get to track disease progression personalised to a patient, you get appropriate therapy at the right time”

To progress the idea, Mohit enlisted the help of Scientia Professors Nigel Lovell and Ewa Goldys, colleagues in the Graduate School of Biomedical Engineering (GSBmE). Nigel is an expert in medical device design and neurostimulation, while Ewa is an expert in nanoscale biophotonics, examining the colour of cells under fluorescent microscopes to learn detailed information about their biochemistry. 

“We reached out to Ewa, and particularly Dr Fei Deng who is in her team, and said, ‘You know everything there is to know about chemical sensors. We know everything there is to know about neurostimulation. We've spoken to gastroenterologists and, from the clinical perspective, we've established that there is a need for this. Now, let's get together to try and solve this’.”

Dr Tianruo Guo, a GSBmE colleague with expertise in computational and biological modelling, was also enlisted to the project. It was he who developed the animal models the team has been using to test the biosensors and associated technologies in a laboratory setting. It’s likely to be another five years or more before the system is trialled in humans. 

"It's very difficult to predict how long it will take us to do this, but I am ready to spend another 20 years on this, to see how encouraging the results will be, and how our work will improve patients' lives," says Tianruo. 

Like his colleague, Mohit is optimistic and passionate about the potential impact of AutoGut.

“I think the real impact is quality of life,” he says. “When you have an intervention that improves daily living, daily function, that's when you can say, ‘I've made a real impact’.”