65th Edition – February 2017

New K4DD math formula predicts duration of potential drug effect

When researchers assess potential new drug candidates, it is not only important for them to know whether a particular drug molecule will bind with its biological target in the body, but also with what strength and speed this binding will occur. If the binding is weak and short-lived or it takes too long for the molecule to bind with the receptor, the drug won’t be very effective in treating patients. In order to improve the assessment of potential new medicines, K4DD project fellow Wilbert de Witte from the Leiden University has published a new mathematical model which predicts how long a drug effect will last. The model takes into account several important variables such as the concentration of the drug in the body and its rate of binding and unbinding with the biological target, and analyses them in order to predict the duration of the potential drug effect. This mathematical approximation, which was published recently in the journal Trends in Pharmacological Sciences, gives an idea earlier in the drug development process on whether a drug is worth pursuing or not. It has the potential to reduce waste and increase the likelihood of getting better and safer drug candidates for the benefit of patients. ‘Even though only one partner is responsible for this paper, the idea to initiate this particular approach was created during discussions within the consortium,’ said Tale Sliedrecht of Lygature, one of the K4DD project partners. ‘By creating an open, pre-competitive environment, researchers from different areas were able to share their insights and needs. The model we came up with is quite significant: the study has led to a lot of debate within the consortium and was highly appreciated by scientists in K4DD’. The study contributes to the overall goal of the K4DD project which is to improve our understanding of how potential drugs bind with their target, and develop methods and tools to allow researchers to study drug-target interactions with greater ease.

StemBANCC and EBiSC contribute to the understanding of a rare pain disease

One of the biggest challenges in drug development is finding ways to translate results from early laboratory tests to human patients. Pluripotent stem cells derived from human patients might hold the key to this translational puzzle, and a new IMI study confirms this potential. In a unique collaboration, both IMI’s EBiSC and StemBANCC project teams contributed to a study led by one of their industrial project partners, Pfizer. The study set out to improve the understanding of a rare pain disease called inherited erythromelalgia (IEM). IEM is a chronic condition with no adequate medical treatment, in which patients suffer from extreme pain that is made worse by heat. The disease is caused by a mutation in a gene leading to overactivity of a sodium channel in patients’ sensory neurons. Pfizer scientists examined if a new experimental drug could block this sodium channel and reduce the pain experienced by IEM patients. When tested on five patients, results indicated that the drug reduced pain upon exposure to heat in most sufferers. However, the experiment didn’t end there. The same patients allowed scientists to take their blood cells and transform them into pluripotent stem cells, which were deposited in the EBiSC project stem cell bank. Next, the StemBANCC scientists turned some of those stem cells into sensory neurons and studied their characteristics in a lab. Prior to treatment, the neurons showed hyper-excitability and an unusual response to heat: the more severe the disease was in a patient, the more the neurons became hyper-excited. When the same neurons were treated with the experimental drug, the hyper-excitability diminished, mimicking the drug effect that occurred in patients. 'This is an exciting study,' said Andrea Weston, Pfizer’s scientific lead for StemBANCC and EBiSC projects. 'Rarely is it possible for drug developers to be able to study the drug responses of the actual, relevant cells from individual patients who are involved in clinical trials of the same experimental drug. These results illustrate that stem cell technology has the potential to transform the way in which drugs are made, enabling scientists to make them much more precise and tailored to individual patients. This is also a good example of how technology can bridge the translational gap between preclinical models and clinical evaluation. The study was facilitated by the collaborative nature of IMI’s projects, and wouldn’t have been possible without the open exchange of knowledge and ideas between different project partners.’

CHEM21 method could cut production costs of essential anti-fungal medicine

Scientists from the IMI project CHEM21 have developed a new, more efficient way of producing flucytosine, a medicine used to treat a common and often deadly fungal form of meningitis in people with HIV / AIDS. The new method, which is described in a paper in Organic Process Research & Development (OPR&D), is expected to decrease drastically costs of production, and so make the medicine more affordable for the many people with HIV/AIDS who live in low income countries.

Flucytosine is very expensive, as its patented manufacture involves carrying out a sequence of four chemical reactions. That could now change thanks CHEM21 scientists from the University of Durham in the UK, who have cut the number of reactions needed from four to one. Because it involves just one selective reaction instead of four, the new method uses significantly less energy and raw materials and produces less waste than conventional techniques to manufacture flucytosine. It is also less expensive. Pharmaceutical company Sanofi, which is also part of CHEM21, contracted MEPI, a French non-profit association, to investigate ways to scale up the process. With input from scientists from Durham and Sanofi, MEPI succeeded in setting up a small reactor capable of producing 1 kg per day of raw material. The next challenge will be for the team at Sanofi to transform the raw material into an active medicine that meets international standards. The University of Durham and Sanofi will also work on a technical and economic evaluation of the process. Meanwhile, the University of Durham has applied for a patent for the technique. The hopes of the team are summed up in the closing paragraph of the OPR&D paper: ‘We envisage that this one-step low cost synthesis of flucytosine will help to raise awareness of the neglected [cryptococcal meningitis] health epidemic and ultimately contribute to meeting the urgent requirement for large quantities of flucytosine for low income nations.’

EUPATI patient expert training course - applications open!

Applications are now open for the third cycle of the EUPATI Expert Training Course, which will run from September 2017 to December 2018. The course is an exciting and unique opportunity that offers patient advocates expert-level training in medicines research and development, specifically tailored for them. The course features a mix of online and face-to-face learning and includes modules on: discovery of medicines & planning of medicines development; non-clinical testing and pharmaceutical development; exploratory and confirmatory clinical development; clinical trials; regulatory affairs, medicinal product safety, pharmacovigilance and pharmacoepidemiology; health technology assessment principles and practices. The deadline for applications is 31 March 2017.

Join eTRIKS for the Bioinformatics and Translational Research 2017 meeting

IMI’s eTRIKS project will hold a meeting on bioinformatics and translational research in Barcelona, Spain on 15-16 May 2017. The datasets that are generated today are complex, and involve many different types of data. The consequence is that the integration of multiple types expertise is necessary. Over the last 4 years, the eTRIKS project has helped 41 translational research projects to get more value out of their data. During that time, it has become apparent that many scientists are simply not aware about the data infrastructure that is available for translational research. With that in mind, the two main themes of the meeting are:

• understanding the landscape of bioinformatics infrastructure and how to reduce fragmentation;
• giving translational researchers the knowledge and the tools they need to collaborate on making sense of translational research data faster.

At the event, data scientists and translational researchers will work together to build a common understanding of today’s research data challenges. The aim is to find ways to help fulfil the promise of better health through the optimal use of data. The event will therefore be of significant value to anyone involved in research data or in developing tools to manage research data.

Registration is free via the event webpage

Apply for a European master programme in drug safety

Registration is now open for the Eu2P Master programme in pharmacovigilance and pharmacoepidemiology for the academic year 2017-2018. The Eu2P Master is an academic post-graduate training that leads to an MSc degree jointly awarded by the six European Universities working together as Eu2P partners. The deadline for applications is 25 June 2017. IMI’s Eu2P project runs numerous courses covering various aspects of medicines research and development, including pharmacovigilance. The courses range from short, ‘bite-sized’ online courses to full Master’s programmes. Details of all courses offered as well as information on how to apply can be found on the project website.