Amber Therapeutics, a University of Oxford spinout developing intelligent bioelectrical therapies, applied the Picostim-DyNeuMo research system developed in collaboration with Bioinduction Ltd. The Amber study (AURA-2; NCT05241379) represents the latest use of the Picostim-DyNeuMo research platform, which was first implanted at Oxford last year for the treatment of Parkinson's like multiple system atrophy.
The Picostim-DyNeuMo research system toolbox was developed as a general-purpose bioelectronic therapy development platform. For the AURA-2 study, leads are placed along the pudendal nerve and the implanted system provides stimulation patterns under control of the research participant.
This research is supported by the NIHR Oxford Biomedical Research Centre (BRC). This kind of neuromodulation is an important area of research in the BRC's new Surgical Innovation, Technology and Evaluation Theme.
Urinary incontinence is a debilitating medical condition that affects 8.5 per cent of the global population. It can bring about a sense of loss of control and shame, leading to isolation and depression. Charles Knowles, Chief Medical Officer of Amber TX and Professor of Surgery at Queen Mary University of London, states: 'Urinary incontinence is one of the most common medical problems in humans. It causes misery for millions of men and women worldwide. Amber's therapy represents the first advanced therapy directed to mixed urinary incontinence. Our study, to determine if this new treatment is safe, will be a major step forward in a field that has seen little real innovation for over a quarter of a century.'
Amber Therapeutics uses its expertise in 'closed-loop neuromodulation' to transform clinical outcomes in patients with functional disorders of the peripheral nervous system. Closed-loop neuromodulation is a type of therapy that adjusts its stimulation parameters according to measurements of the nervous system's needs in real time.
In the AURA-2 study, investigators are exploring how to directly regulate the urge to empty the bladder ('urge incontinence') and also increase resistance to urine leakage caused by activities such as coughing or lifting (mixed urinary incontinence'). The implanted device can sense, interpret, adapt and respond to individual patient commands in an attempt to restore normal bladder function. The device is inserted in participants' pelvic region using a minimally invasive surgical procedure that accesses and targets the pudendal nerve – the nerve that directly controls continence.
In partnership with clinicians, we can create novel adaptive, reflex-like, algorithms for exploring new therapies.
- Professor Tim Denison
Stimulation-only neuromodulation therapies targeting the sacral nerve do already exist for urge urinary incontinence, which represents about 11 per cent of all urinary incontinence. However, with only about 50,000 implants inserted per year in the US (where 6.8 million people could potentially benefit), this market is highly under-penetrated. Until now there has not been a single therapy on the market or in development for mixed urinary incontinence, which is more common (36 per cent of all urinary incontinence).
Stefan De Wachter, Professor of Urology at Antwerp University and leading investigator for the study added: 'Most of the current available implanted therapies for incontinence are static (tapes, slings) or can only influence the bladder indirectly (such as sacral or tibial stimulation). In the AURA-2 trial, we stimulate the pudendal nerve, the natural pathway of continence control, and can reinforce the existing physiologic reflexes when they are needed. With our adaptive therapy, we finally have the potential to control both forms of continence: relaxing the bladder to treat urge and closing the sphincter to treat stress incontinence.'
The clinical trial
To date, five participants have been safely implanted with the Amber-UI system with the adaptive algorithm activated and running continuously in an at-home setting. The remaining participants will be enrolled during the first half of 2023. Early indications confirming the feasibility of the surgical procedure and therapy are very promising. The study is expected to conclude towards the end of 2023, with learnings used to improve and optimise the Amber-UI therapy in preparation for a large-scale trial.
Amber Therapeutics started its ground-breaking first-in-human study in late 2022. Oxford Science Enterprises, 8VC and a UKRI Biomedical Catalyst grant provided seed funding for the development work. The trial will evaluate the safety and pilot efficacy of the therapy in 15 women. It is being conducted at the University Hospital Antwerp (Belgium) by Stefan De Wachter, Professor of Urology.
To assist with the trial, Bristol-based Bioinduction Limited have provided Amber Therapeutics with their miniaturised 'brain pacemaker', the Picostim-DyNeuMo. The Picostim-DyNeuMo was developed in collaboration with the University of Oxford and a network of UK academic partners to serve as a general-purpose therapy research system, leveraging Bioinduction Ltd's Picostim DBS stimulation device.
Tim Denison is Chief Scientific Officer of Amber Therapeutics and RAEng Chair in Emerging Technology at the Department of Engineering Science and Nuffield Department of Clinical Neurosciences, University of Oxford. He said: 'Modern bioelectronic systems have the unique capability to measure physiological signals and adjust stimulation in real-time. In partnership with clinicians, we can create novel adaptive, reflex-like, algorithms for exploring new therapies. The flexibility of these systems allows us to use software updates to configure to different disease states, and the AURA-2 study builds on the prior trial in Multiple System Atrophy, and paves the way for emerging therapies in generalized epilepsy and chronic pain. We are grateful for our partnership and collaboration with Bioinduction, and their support of the state-of-the-art Picostim-DyNeuMo research system, which has allowed us to rapidly explore our first UI therapy concept'.
Ivor Gillbe is the co-Founder and Director of Bioinduction Ltd. He added 'This is an exciting time for Bioinduction and the UK bioelectronic medicines industry. Together, we believe we can grow the economy while accelerating the research around neuromodulation which will address healthcare conditions that significantly impact our ageing society.'