Abstract
Interview by Rona Williamson, Commissioning Editor
Henrik Klitgaard, PhD, is currently Vice-President, UCB Fellow, Neurosciences Therapeutic Area and is based in Braine-l’Alleud, Belgium. He received a PhD in Human Physiology in 1989 at the August Krogh Institute at the University of Copenhagen (Denmark). During his university career, Klitgaard worked at the Pasteur Institute in Paris (France) and at Harvard University (MA, USA). Klitgaard is a leading figure in the epilepsy research community, thanks to more than 80 peer-reviewed papers and 15 reviews and book chapters, as well as frequent lectures at top neuroscience and epilepsy science meetings. His memberships and accolades include a position on the US National Institute of Health’s epilepsy advisory committee, membership of the Neurobiology Committees of both the International League Against Epilepsy and American Epilepsy Society and a seat on the Scientific Advisory Committee of the patient organization C.U.R.E. (Citizens United for Research in Epilepsy). For more than two decades, Klitgaard has conducted antiepileptic drug discovery in the pharmaceutical industry. He has contributed numerous publications on basic and applied aspects of epilepsy research and has frequently been an invited speaker at epilepsy congresses and meetings. During his career in the pharmaceutical industry, Klitgaard has been involved in the discovery and development of antiepileptic drugs at both Novo Nordisk A/S and UCB Pharma. He is also currently involved in the development of two clinical and several preclinical AED candidates.
Can you give us a little more information on your background and how you came to specialize in the field of antiepileptic therapeutics?
I have a PhD in Biology and 22 years in the pharmaceutical industry where I have always focused on epilepsy research and antiepileptic drug discovery. It has always been a scientific area that has held a lot of interest for me, if not passion, and I have enjoyed every aspect of being involved in antiepileptic drug discovery.
You are a Fellow at UCB, can you tell me more about what the company wishes to achieve in the next 5 years and what you think has been the company’s greatest achievement to date?
UCB has a commitment to being at the cutting-edge of science and the UCB Fellows must facilitate and support internal efforts of research and drug discovery. We focus on creating ‘super-networks’ which consist of high-standing academics and we interact optimally with these academic groups to be at the cutting-edge level of science. Every drug that impacts a patient’s life is an achievement independent of therapy area. UCB focuses on providing therapies in areas with significant unmet medical need, which implies that every drug that reaches a patient is providing a significant benefit. In general that is for me the aim, and what we try to achieve at UCB.
How do you feel the UCB award, presented every 3 years under the patronage of the Queen Elizabeth Medical Foundation, supports and promotes neuroscience research?
The award is given to scientists that have performed outstanding scientific or clinical research in the field of epilepsy. By supporting this award we are also supporting the scientific activities in the field of epilepsy with the hope that progress will further unravel understanding of the pathophysiology of the disease and thereby provide the means to identify improved treatments.
If we can now move onto discussing Keppra, the anticonvulsant that you were heavily involved in developing, what effect do you think its introduction has had in the field of epilepsy therapy?
First, I would like to address some basic facts of the disease. Epilepsy is one of the most common diseases of the central nervous system and it actually afflicts approximately 50 million people worldwide. A recent paper has been published highlighting the magnitude of the unmet medical need in epilepsy. This magnitude is of such significance, that there are calls for epilepsy to be considered a global health issue. Epilepsy is a chronic disease but we have treatments for it. The first, introduced in 1857, was potassium bromide, and ever since we have seen a number of epileptic drugs becoming available on the market. Today, we have more than 20 drugs on the market in western European countries. However, despite the fact that we have an armamentarium of antiepileptic drugs there still remains approximately 30% of epilepsy patients who are refractory, meaning that even though they receive therapy with often a significant number of drugs they still have seizures. None of the drugs available provide any preventive or curative treatment of the disease so we still have a significant unmet medical need. At UCB we are very committed to antiepileptic drug discovery and development, and very committed to not just pipeline management but also to providing future drugs. The experience with Keppra, particularly, was a learning process for us. When we first tested the compound it was inactive in the preclinical model studies normally used to identify antiepileptic drugs, but we believed to have all the data supporting Keppra as an antiepileptic drug so we began to develop new paradigms and new models and actually proved in the end that Keppra was active in different preclinical models that reflects various aspects of the pathophysiology. Having proven that Keppra had promising activity preclinically, we also had to discover the molecular mechanism of action. Following several years of scientific work, we identified that Keppra has a completely novel mechanism of action by interfering with the so-called synaptic vesicle protein 2A, which is related to the release of neurotransmitters between neurons in the brain. That lesson taught us that if you dare to invest in novel preclinical models and in novel biology then you may also be able to supply drugs to the market that can provide a very significant patient benefit. Realizing that we have a significant unmet need remaining in the treatment of epilepsy we have decided, at UCB, to really focus our science efforts on trying to identify novel drugs that interfere with the underlying mechanisms of drug-refractory epilepsy or the disease itself. That’s really what we are focused on. Then we try to capitalize on our academic super-networks and collaborations with different academic groups to further understand the pathophysiology and identify novel targets and paradigms for model testing, in order to move forward with the hopes that we can identify drugs that can meet the significant unmet medical need of drug-refractory epilepsy or prevent or cure the disease.
Overall, looking at the field of antiepileptics, where do you feel that it is advancing towards?
I think the field is realizing that recent advances in understanding the pathophysiology permit us to embark on the identification of drugs that really treat the issue of drug-refractory epilepsy or new treatments that really can interfere with the underlying cause of the disease, so we can begin to identify treatments that can either prevent or cure the disease. UCB is very vocal on that need and committed to contributing everything we can to achieve this goal.
Finally, do you have any words of advice you would give a young researcher entering the field of neurotherapeutics?
I have one single word that always worked for me and that is ‘passion’. Follow your passion and you will be able to perform cutting-edge science, even though you will encounter a lot of challenges you should persist and in the end you will prevail.
Financial & competing interests disclosure
The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.