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How Leiden's drug pioneers have switched to Covid research

From studying molecules in the blood of corona patients to developing a new concept for vaccines. The Leiden Academic Centre for Drug Research (LACDR) has transformed many ongoing projects into Covid research projects. Hubertus Irth, scientific director of LACDR, talks about the role of his institute and the scores of collaboration projects at Leiden Bioscience Park (LBSP). ‘This pandemic can only be beaten if the entire biomedical world works together.’

The researchers from LACDR watched the swift emergence of coronavirus at the start of this year with increasing concern. Within a matter of weeks, six groups had transformed their ongoing research projects into Covid ones. Irth: ‘LACDR doesn’t usually work on one particular disease such as Alzheimer’s or cancer. We work on new concepts and validation methods for vaccinations, for instance. But we’re now looking at how we can apply these methods to Covid-19.’ His institute belongs to the Faculty of Science and has been working closely with various partners at LBSP (see below) for years already. ‘These intensive partnerships are more than proving their worth.’

‘These intensive partnerships are more than proving their worth.’

Predicting disease progression

The initiative to adapt existing research lay with the individual research groups, and Irth applauds this. ‘This pandemic can only be beaten if the whole biomedical world works together. LACDR can help solve a very complex puzzle one piece at a time.’ One promising project is the lab research of Thomas Hankemeier, Professor of Analytical BioSciences. His group is studying molecules in the blood of Covid-19 patients that can predict the disease’s progression. This would make it possible to predict the severity of a patient’s symptoms at an early stage already. Rapid medication might then help control certain unwanted processes. The group has already discovered the first patterns in patient profiles. The research is in collaboration with three teaching hospitals: the LUMC, Erasmus MC and UMC Utrecht. Irth: ‘It didn’t take long for the researchers to find one another because they have already worked together on other projects.’

Drug dosage app

LACDR is also researching the dosage of drugs that were not developed for Covid-19 but may have a beneficial effect. Irth: ‘An 80-year-old needs a different dose from a 25-year-old. We are trying to make the treatment as personalised as possible.’ Pharmacologist Coen van Hasselt and his group developed Covid19pkpd.eu, an app that doctors can use to determine a safe and effective dose of potential drugs. Van Hasselt usually researches the dosage of antibiotics.

New vaccine concept

The corona pandemic has inspired dozens of candidate vaccines around the world, most of which aim to produce neutralising antibodies. LACDR research into other respiratory viruses has shown that cytotoxic T-cells and local immunity in the airways can prevent reinfection. Researcher Bram Slütter’s group is laying the groundwork for a vaccine that uses these extra layers of protective. This requires a somewhat different formula and drug delivery system. These are just some of the LACDR’s innovative Covid projects.

‘We try to be five to ten years ahead of the pharmaceutical industry.’ 

Speed versus safety

It can easily take 12 years to develop a new drug. In this corona crisis the different parties – academia, industry and government – are trying to smash this timeframe. What is Irth’s opinion about this? ‘Speed is of the essence given the gravity of the situation, but safety still has to come first. Imagine that everyone on the planet is inoculated. If this has a fatal side-effect in 0.1% of these people, you’re talking about millions of deaths. That’s what makes testing so complicated. The larger the number of patients, the harder it is to design tests. They obviously need to have diverse test subjects so that you can discover as many side-effects as possible.’ However, Irth thinks that a corona vaccine won’t take too long. ‘Given all the efforts and investment, I would hope it would be sometime next year, but we scientists will continue to keep a critical eye on the process. Who knows? Perhaps the vaccine will come from Leiden, from Janssen Vaccines, the company that we are working closely with on other programmes.’ (see below)

Pioneering

LACDR does both applied and fundamental research. What is the role of Irth’s institute in the medical world? Irth: ‘Drug development is a mind-blowingly expensive process that costs an average of 1.5 billion euros. It’s inconceivable that an academic research institute like us could achieve that. We try to be five to ten years ahead of the pharmaceutical industry and develop new methods and drugs that can be passed on to other parties at a later stage.’ 

Students conduct Covid research

Leiden has the largest Bio-Pharmaceutical Sciences programme in the Netherlands and the LACDR deliberately involves many students in the many research projects. Two hundred bachelor’s students were set to start their research project in March, and many of them are now doing Covid research. Irth: ‘With the aid of literature reviews, they are developing a new concept for a corona vaccine, for instance, and are mainly focusing on particular aspects such as how to improve its administration. They are also discovering really interesting information, which is exciting and educational for them. Coming up with an idea is one thing, but the first steps in the lab are when the real work begins.’

‘Being able to pop into each other’s lab really helps.’

Catalyst

The LACDR’s LBSP location is an advantage, says Irth. ‘In terms of size alone, we are one of the larger parks in Europe. We are in a global competition and the entire chain is represented here in Leiden – from the lab to the pharmaceutical companies and the LUMC. Being able to pop into each other’s lab for measurements or blood samples, for instance, really helps. This physical proximity is an enormous catalyst.’ 

Collaboration at the LBSP
Before a drug is available to a patient, an entire process has been followed: from fundamental science to clinical tests to production. The University, the LUMC and the businesses at the LBSP work closely together to make the hunt for new drugs as efficient as possible. Alongside the LUMC, LACDR is working on research programmes with, for instance, Janssen Vaccines, the company that is going to test a candidate vaccine for Covid-19 on humans in July this year. It also works with other large pharmaceutical companies such as Galapagos and with biotech companies such as Toxys, OcellO and MIMETAS that can trace some of their roots back to the LACDR. MIMETAS puts human cells on a chip, a revolutionary technology that could replace some human and animal tests. Researchers who work there received their PhD at LACDR in 2010 and went on to start MIMETAS, which now employs a staff of around 100.

Also see the Effective drug development dossier.

Text: Linda van Putten

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