I Peeked into a World That Was Hidden to Me, Says Vítězslav Bryja

How to make cells change their behaviour and cure a patient with a serious disease? That’s what the scientists from the Faculty of Science are trying to solve. Chemists and biologists have joined forces and are working on developing inhibitors of the casein kinase 1 enzyme which plays a crucial role in the progress of chronic lymphocytic leukemia (CLL) and, potentially, other diseases. They’re currently looking for an investor. Where are the limits of academic research and what is a scientist’s view on the world of business? That’s what we talked about with one of the researchers – Assoc. Prof. Vítězslav Bryja.

21 May 2019 Iveta Zieglová

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In 2016, we conducted an interview regarding your research into casein kinase 1. Back then the pharmaceutical companies basically sent you back to the lab because they weren’t interested in a research based on a publicly available substance. What has changed since then?

We’ve managed to do a lot. Back then we decided to create a family of entirely new compounds that would be owned by the university, which turned out to be the right decision. We’ve tried two approaches. One of them was computational but it turned out to be a dead end. The second one was based on organic synthesis of new molecules. We used the crystal structure of casein kinase 1 with a generally accessible inhibitor and we tried to use the knowledge we gained to create a better inhibitor which would bond using a different mechanism, thus allowing us to patent the compound.

Was this approach successful?

One of the compounds, which was originally a bit of a makeweight, manifested some unusually useful properties – increased specificity, which means it didn’t inhibit other enzymes, and better efficiency. The team of physicists led by Assoc. Prof. Kamil Paruch that carries out all the syntheses has found out that the part of the compound called central pharmacophore is truly unique; we should therefore be able to patent the inhibitor.

What phase is the research currently in?

To this day we’ve come up with over 150 compounds out of which we’re picking the best. The purpose of the inhibitor is also important. When we’re talking about casein kinase 1, we actually mean a family of six enzymes, and blocking each of them may be used for different purposes. At the same time we were trying to understand how our compounds work. We found out that they bond in a unique way which means we know which parts of the compound we cannot touch and which, on the other hand, can be further modified to exhibit different chemical or pharmacological properties.

Three years ago we talked only about treating CLL. Now it seems that the inhibitors could help treating a number of other diseases. Where do you see their potential?

Our know-how is still CLL where we discovered the role of the enzyme. However, we’ve had an overview carried out of other companies that work with casein kinase 1 and there are other possibilities. Most recently treatment for AML, that is acute myeloid leukemia, so far an incurable disease. Then there are solid tumours; with those the Wnt signaling pathway is known to play a significant role. We’re studying it and we can inhibit it using our compounds. Another group of diseases where casein kinase could be used are neurodegenerative diseases. But as I said before, our “playfield” is still mostly CLL. Other potential research directions would depend on the investors and their idea of the path we should take. We’re currently looking for a partner who would be interested in developing our compounds and get them into clinical trials because we’ll soon reach the limits of academic research.

Where do you see the limits of academic research?

I believe that we’ll be able to identify among our compounds a suitable candidate and verify its biological effects. However, getting the research beyond cells and mice is simply not in our power. A mouse weighs 20 grams so if we use a 20-kilogram animal or an 80-kilogram human for the tests we’ll need a much larger amount of the compound. That would be a strain on our capacities, funding, and technological limits. Another problem is unstable funding. We depend on grants out of which we have to make a contribution to the university’s central budget and we need this money. Stabilizing our funding is, therefore, one of the key elements of success. Research such as ours is costly, there is nothing we can do about that.

This is the first research of yours during which you came into contact with investors. How would you describe this experience?

Investors are interested in different things than academicians. This is hardly surprising but experiencing it first hand still took me aback. I found out there was an entire hidden world – the world of information analysis that you won’t find in any academic journal. There is a lot of extremely expensive information gathering and processing; however, these things interest the investors greatly – analyses that examine the potential of our compounds, who else is working on similar research, what is the competition like, how many people already failed. One realizes what the companies seek and what parameters our compounds should meet.

Have you got some feedback from the companies? Are they interested?

I believe we have a unique, quality product and we know its potential. Several recent meetings with investors have supported me in being optimistic about the success of our technology.

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