Professor Fiona Ducotterd on the process of drug discovery
Professor Fiona Ducotterd PhD CSAP is Chief Scientific Officer at the Alzheimer’s Research UK UCL Drug Discovery Institute (UDDI).
What first attracted you to the area of neuroscience and drug discovery?
I was always interested in the mechanisms that cause disease. As a teenager, I babysat for an adorable three-year-old with cystic fibrosis. I wanted to understand how a single genetic mutation caused such severe symptoms for this perfect little girl and was inspired to study molecular biology at the University in Edinburgh.
Around that time, my granny was diagnosed with Alzheimer’s and as I watched her memories and executive functions fade I also got an opportunity in my third year as an undergraduate trainee to work in a pharmaceutical company on new medicines for Alzheimer’s disease. That personal connection to the lab work at home and my curiosity about the brain and how it changes in disease really set a fire inside me.
All of us are waiting for better treatments for people we love affected by Alzheimer’s and other dementias but there is a lot of work to do. At the UDDI we are trying to address very difficult problems as brain diseases are multifactorial and sometimes the data we generate isn’t what we hoped for. That’s when all the personal stories inspire us to keep the work moving forward.
Having a career in drug discovery is such a privilege and at the UDDI we sit in the heart of the emerging innovative discoveries at UCL, with resources from ARUK to translate those rapidly into therapies.
Can you tell us about your current projects?
The UDDI lab is set up like a biotechnology company with highly skilled biologists, pharmacologists and medicinal chemists and industry-standard technical equipment. We have a generous core grant from Alzheimer’s Research UK that enables us to work on a portfolio of projects that are balanced across very new, emerging ideas around disease biology to more established novel targets where we have already identified small molecules through screening campaigns.
We have a remit to take cutting edge new ideas from our academic innovator colleagues and turn them into tractable translational drug discovery campaigns. We work closely with our collaborators to take the best science and combine it with our industry expertise to build targeted and focused small molecule drug discovery programmes.
We work across neurodegenerative diseases and have projects that target the underlying biology of Alzheimer’s, Parkinson’s, motor neurone, Huntington’s and also general disease mechanisms. Working across diseases allows us to build data on commonalities and differences across them to build a broader toolbox of future treatment options. We are fortunate to collaborate with amazing academic experts across UCL, the UKDRI, the UK and internationally and also have partnerships with industry.
Some of our projects are funded specifically by translational research awards that allow us to accelerate the studies by turning up resources. Working closely with Alzheimer’s Research UK allows us to get a lot of insight from patients and families that help inform our work and our plans to move from bench to bedside. Our portfolio is changing all the time as we stop projects that don’t make the progress we need, and move others on to the next steps in the process or try to partner them with companies to take them forward.
What are the main challenges in developing drugs to treat neurodegenerative conditions like dementia?
The brain is the most complex organ and we have to treat the disease without causing any abhorrent activity or behaviour which means some targets are not feasible. It is hard to get therapeutics into the brain and it also hard to model the brain in a dish.
The lack of translational models, the wrong questions being asked of models, and the challenge with accessing human biology on the brain make it really challenging but the technology is improving all the time as is our understanding of the human disease from clinical research.
How will UCL’s new centre for neuroscience support translational work and drug discovery?
The new centre will put us at the heart of UCL’s cutting edge academic innovators, world-leading clinicians and also closer to patients. This unique place where we can work together without boundaries and in collaborative, open spaces will facilitate the firepower that comes from sharing ideas.
I am excited to be there as the location will enable us to have more conversations with researchers and progress more targets through our portfolio process. We plan to be the partner of choice for translating ideas into new therapeutics working closely with the broader team.
The discovery of drugs such as lecanemab has been heralded as the beginning of the end for Alzheimer’s. To what extent do you think we are entering a new era when it comes to tackling neurodegenerative diseases?
This is a very important beginning for the field and increases the hope that we can move the needle on this devastating disease. It really is a great start. The amyloid lowering therapies have shown we can change the trajectory of the disease modestly in some patients. There is still a lot of work to do to make more effective treatments that are accessible to all patients and we are all in to do that in the UDDI.
It is unlikely a single therapy will treat Alzheimer’s or other neurodegenerative diseases that are complex and multifactorial. Early biomarkers of disease – presymptomatic ones, that allow interventions prior to cognitive decline – will hopefully allow us to prevent before it is too late for full reversal of symptoms.
With continued investment in basic research to validate novel disease mechanisms, human studies to understand the heterogeneity and homogeneity of different biomarker trajectories over the course of the disease, and a toolbox of treatments with clear labels on when to intervene based on biomarkers there is a lot of hope for the future.
Right now we need to accelerate and invest to get more therapeutics progressed towards patients – and also better biomarkers to predict where the patient is in the disease trajectory, what treatment to use and whether it works.
About the Alzheimer's Research UK UCL Drug Discovery Institute
The Alzheimer’s Research UK (ARUK) Drug Discovery Institute (UDDI) is a member of the ARUK flagship Drug Discovery Alliance along with the Oxford and Cambridge Alborada DDIs, founded in 2015. It was founded to address the exit of neurology-focused pharmaceutical companies in the UK and to provide pharma-trained industry scientists in the UK with the resources and infrastructure to take new innovations emerging from the world-leading academic centres of UCL, Oxford and Cambridge and the wider UK network and translate them into next-generation medicines for dementias.
The DDA teams are focused on projects that are emerging and novel and have downstream commercial viability for pharma licensing to take through clinical development to patients.
The UDDI has a broad-spectrum portfolio of projects targeting new biology identified through human genetics or other translational studies in academic laboratories.
About Professor Fiona Ducotterd
Professor Fiona Ducotterd PhD CSAP is Chief Scientific Officer at the Alzheimer’s Research UK UCL Drug Discovery Institute (UDDI). Professor Ducotterd is a trained neuroscientist and drug discovery executive with >20 years of global experience spanning therapeutics research and development, business development and strategic alliances in pharma (e.g. MSD, GSK, Eisai), biotech (e.g. Vertex, Mindset, Shackelford) and academia (UCL) in the UK, Japan, China, the USA and Canada.
At the UDDI, she leads a team of 30 multidisciplinary scientists discovering new medicines for neurodegenerative diseases in partnerships with leading academic innovators as well as industry alliances and spin out companies. Fiona has a BSc in Molecular Biology from the University of Edinburgh and a PhD in Neuroscience from the University of Newcastle upon Tyne in the UK and is a Chartered Alliance Management Professional. She is a mentor and coach to a range of scientists and also Mum to toddler, Isla, and fur baby, Yuna.