In epilepsy, certain nerve cells are hyperactive, which can lead to various types of epileptic seizure. Most traditional antiepileptic drugs block the function of sodium channels, in order to reduce the excitability of the cells and to reduce the rate of nerve impulses that are transmitted.
“We are searching for substances that open the potassium channels instead. If the potassium channels are opened, the activity of the nerve cell is reduced, which acts as a brake in the nervous system”, says Fredrik Elinder, professor at the Department of Clinical and Experimental Medicine.
Project manager Nina Ottosson and professor Fredrik Elinder develop new drugs against epilepsy. Photo credit: Susanna Lönnqvist Sodium and potassium channels are ion channels, which are specialised proteins that are located in cell membranes and form pores that can allow or prevent the passage of ions. The fluxes of ions into and out of nerve cells is the basis of the electrical excitability that characterises the nervous system.
The most common way to block the sodium channels is to plug the ion conducting pore. Project manager Nina Ottosson, together with Fredrik Elinder, focusses instead on other parts of the potassium channel than its pore. They have identified other locations on the potassium channel at which certain substances can bind and cause the channel to open.
Admission to use the DDD platform as a full program follows a careful review of the various parts of the project and assessments of its risks and feasibility. Nina Ottosson welcomes the very detailed examination of the project by DDD.
“The work that the DDD personnel put into this and the plan of action they drew up will be useful for us for at least the coming two years. The application meant a lot of work for us as well, everything from creating a strategic commercialisation plan to attempting to predict, in collaboration with experts at DDD, any toxicological risks of our substances”, says Nina Ottosson.
The DDD platform can offer help at various pre-clinical phases of drug development, before it is to be used in clinical trials and tested on humans. The pathway to clinical trials is long, measured in both time and resources. Before clinical trials can start, the project must be able to demonstrate proof of concept, and it is during this period that DDD offers expertise.
“A substance must be tested in many different ways before clinical trials can start: how it binds, how it is metabolised, and how it behaves in the body. We receive a lot of help from chemists and toxicologists during this process, working with the practical experiments. The platform can also help with important strategic decisions, for example regarding patenting”, says Nina Ottosson.
Fredrik Elinder agrees.
“In the matter of strategy, they also help to decide how to interest future investors. It’s easy to focus on the experimental part of the project, and without the contribution from DDD it’s possible that we wouldn’t have been able to answer questions that investors pose in the future.”
At the same time, admission to the platform will make it possible to carry out the preclinical tests within academia world, and the need to engage external financers is delayed.
“The support means that we don’t have to focus on seeking investors during this early stage of the project. This is something we otherwise would have been compelled to do in order to make many of the pre-clinical experiments possible”, says Nina Ottosson.
Approaching clinical trials
Most experts who are part of DDD and work there have a background from the pharmaceuticals industry. Ottosson and Elinder agree that both ways of thinking, the academic and the commercial, are needed in drug development.
“I’m convinced that the academic way of approaching problems and the academic freedom are extremely positive when trying to develop new drugs. At the same time the knowledge and experience within the pharmaceutical industry are invaluable for us in our attempts to succeed”, says Fredrik Elinder.
Nina Ottosson has worked with the underlying idea of the project since 2010, during her time as doctoral student in Fredrik Elinder’s group. She has thoroughly enjoyed taking the project onto the next step, to drug design.
“It’s been great to work with the same molecules, using a completely different approach. This way of working suits me: I can bury myself in the details of research while at the same time facing new challenges in other areas”.
The project is evaluated by DDD every six months, and it is hoped that the collaboration will continue with increased support during the spring of 2019. This would involve establishing a dedicated project group at DDD and setting the strategy for drug development.
SciLifeLab & DDD
SciLifeLab is a national centre for research into the life sciences and biomedicine, and is one of the three largest research infrastructure facilities in Sweden. The Drug Discovery and Development Platform is part of SciLifeLab, but it is an autonomous unit with its own budget. It collaborates closely with the innovation systems in Sweden. Approximately 15% of the projects that apply are admitted to the platform. All drug development supported by DDD is to be carried out within academia, and the intellectual property rights belong to the researchers throughout the process.
In association with the collaboration with DDD, the project has received contributions from the Novo Nordisk Fonden to carry out ion channel measurements in an automated system at the Danish company Sophion A/S.
Translated by George Farrants