Sitting down with… Stefanie Dedeurwaerdere, UCB

MRI of the brain

Stefanie Dedeurwaerdere

Stefanie Dedeurwaerdere is Global Strategy Lead for Pipeline Development in Global Epilepsy & Rare Syndromes at UCB. In her day-to-day role, she is responsible for the development of UCB’s epilepsy discovery strategy, working with researchers to advance understanding of epilepsies while ensuring candidates for a future clinical treatment pipeline to improve the lives of those living with the condition.

LR: Can you share the latest epilepsy research trends?

SD: There are multiple types of epilepsy. We now commonly refer to epilepsy as ‘epilepsies’, with the recognition that it isn’t a singular disease. In addition, for those living with certain, rare epileptic syndromes – seizures are not the only impactful symptom.

With this in mind, there is a trend in research organisations like UCB to build both pre-clinical and clinical research in areas that go beyond anti-seizure treatment and instead redefine patient populations based on mechanisms that explore the root cause of certain epilepsies.

Another trend we are seeing is linked to the increased emphasis on digital technologies and artificial intelligence (AI) to improve efficiencies in the research process, improving the speed of data analysis and allowing lab scientists time to focus on challenging questions.

LR: What are the challenges and opportunities in this field of research?

SD: One of the biggest challenges and opportunities in epilepsies research is the paradigm shift from anti-seizure models that historically have been the key to unlocking new treatments for epilepsies typically targeting the synapse of the neuron or its electrical conductance.

While widening research on anti-seizure medication is important, we need to broaden the scope of research to understand the unmet medical patient needs and investigate the development of potentially disease- modifying treatments that target the disease more holistically.

In order to do this, we must gain a greater understanding of the human pathobiology of epilepsies outside of our typical focus on seizure symptoms, and use this understanding to change our screening cascades, mechanisms of action and drug targets.

As research efforts continue in these areas, there is also the linked hurdle that unlike anti-seizure medicine which typically acts quite instantly on the seizure, more holistic symptoms can be more challenging to measure and often take more time to analyse, meaning research efforts also take more time and increase in complexity.

LR: What is UCB’s current focus on research in this area and are you able to outline any of your drug discovery programmes?

SD: At UCB, we currently have several drug discovery projects running, which we are very excited about. To further increase our understanding of epilepsies, we’ve been collaborating with universities on building one of the largest analyses of human brain tissues from epilepsy patients in the world, including > 200 samples. This in-depth study allows us to comprehend the world of epilepsies as a global brain map, to quantify different subtypes of epilepsy, understanding what they may have in common and what could be unique to specific conditions.

For complex epilepsies, where there is no clear cause or underlying aetiology, the situation is more challenging. Here, we are building on learnings from other epilepsies where tissue is available as well as genetics to help understand universal disease mechanisms across epilepsies.

In addition, we have also developed an artificial intelligence computational framework in collaboration with various academic partners to investigate disease mechanisms and processes that could help us to identify novel areas for future therapeutic entry points.

LR: Can you explain more about UCB’s approach to understanding epilepsy and combining patient knowledge with information on disease pathways and biology?

SD: Over the last decade, patients have been increasingly active and empowered when it comes to decisions concerning their health. Pharmaceutical companies now consider patients as true research partners, working towards a collective goal of progressive treatment and cure.

At UCB, we fully embrace the notion of patient centricity and are integrating the patient voice into our decision-making progress. This helps us to understand the current unmet treatment needs in patient populations. The earlier we can understand the patients’ individual pathways that led to the disease, the greater we can understand specific disease biology.

Research shows us that patient advocates and representatives typically tend to have higher levels of education and medical literacy. However, as part of our commitment to supporting all patients at UCB, it is important to us that we are able to have contact with a truly diverse representation of patients. This helps us to understand the needs of patients throughout all aspects of culture and life, including patients from different ethnic backgrounds, lower socioeconomic statuses, or even those experiencing symptoms such as depression and anxiety.

Lastly, collaboration with community groups and leaders, grass-roots organisations, and patient advocacy groups allows us to understand our diverse patient needs. Ultimately, at UCB, we recognise that dialogue, collaboration, and partnerships are key to us providing greater value to patients; and gathering insights from patients is a key part of that process.

LR: In terms of disease biology, how are you redefining the patient population according to mechanisms?

SD: While typically epilepsy is classified according to seizure subtypes, we envisage that in the future we will include definitions based on underlying pathology. This is already occurring for some of the developmental epileptic encephalopathies for which some are denominated based on the genetic deficit.

Moving beyond anti-seizure medication to explore underlying causes is a hugely complex task, that requires us to look backwards to the pathways that led up to the disease.

Advances in ‘omics’ through higher through-put molecular sequencing techniques and analytical pipelines are supporting this process, capable of revealing the molecular-level changes of genes, proteins and other molecules that can cause neurons to over-fire in parts of the brain.

These new approaches to research allow us to redefine patient populations based on sub-types of associated epilepsies and can open the doors for new ways of approaching treatment in the future.

LR: How will this sector look in 10 years’ time; what type of drug/therapeutics are we likely to see?

SD: If we look across the current clinical development landscape, there are close to 100 interventional trials ongoing (epilepsy, recruiting and non-recruiting active, phase I-III). While the majority still focused on seizure types, this will likely lead to advancements in the quality and global accessibility to anti-seizure treatments in years to come.

Beyond this, several studies exploring more specific genetic indications and syndromes are moving us beyond treating ‘seizure types’, to understand the wider holistic picture of epilepsies.

If we can categorise these epilepsies according to mechanisms and gain a wider understanding of the pathobiology, we can move closer to disease-modifying treatments, and one day, hopefully, a cure in an area of high unmet need, and as a scientist, that is something which truly excites me.

DDW Volume 25 – Issue 1, Winter 2023/2024

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