New drugs for mental illness

20 May 2019

Interview with 

Santiago Lago, Cambridge University

DRUG DISCOVERY

DRUG DISCOVERY

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Mental illness is, unfortunately, very common. And although there are drug treatments for many psychiatric conditions, they all have side effects and very few genuinely new drugs have been discovered in decades. But now that might be about to change. Using blood cells from patients with mental health disorders, scientists at Cambridge University have found a way to identify potential new targets for drug discovery. Katie Haylor spoke to Santiago Lago, who worked on the study. Firstly, Katie asked, why the paucity of new drugs for mental illness?

Santiago – It turns out actually that up to 75 percent of patients do not respond fully to the drugs that exist and this is because we don't really understand what causes the diseases. We don't have very good ways of testing new drugs in the labs. So, for example, you can't really ask a laboratory mouse whether it's depressed. It's not easy to access live brain tissue from patients and also actually when we talk about diseases like schizophrenia we're not talking about a single disease, there are actually many different types of schizophrenia.

Katie - Okay. So, what are you doing differently then? How does your approach work?

Santiago - What we're doing differently is actually using patient blood cells as an accessible way to test new drugs. So, I mentioned that it's difficult to take live brain tissue but it's obviously much easier to take a blood sample and use live blood cells. Blood cells actually share many of the pathways which brain cells use to function. What we're doing here is we're testing those shared pathways to see if they can reveal new drugs. And another thing that we're doing differently is instead of simply counting genes and proteins we're actually focusing on cellular behaviour.

Katie - Can you tell us about what you did in this study, specifically how many people's blood we looking at?

Santiago - So initially we took a cohort of patients with schizophrenia and healthy controls, although that's a very relative term. Who is who is healthy, who is normal? But for the purpose of argument we took a group of 12 patients with schizophrenia and 12 healthy individuals. Then we used robots in the lab to culture their blood cells with a range of chemical compounds. We then painted the cells with fluorescent dyes which allow us to look inside the cell and see how the proteins are behaving differently. And then we measured each individual cell using a laser based technology called flow cytometry. So, this actually allowed us to examine how the blood cells from patients were behaving differently than healthy controls.

Katie - Okay and how are they behaving differently thn?

Santiago – Actually, in a number of ways for the purpose of this study we focused on the most important response, or the one that we saw that was most drastically different in the patients. The cells from schizophrenia patients used calcium in a different way within the cell. So calcium in the cells in our body, it’s a way that the cell communicates inside, and it turns out that when we administered a certain drug to these schizophrenia cells they used calcium differently within the cell.

Katie - And is this new information this calcium response?

Santiago - This particular response is. I mean calcium has been known to be involved in these disorders, but we have discovered a new protein which responds to the calcium differently in patient cells.

Katie - So how could this translate then to finding drugs to treat schizophrenia? What's the next step I guess?

Santiago - So that's really what it's all about. Then what we did was to see which drugs could actually fix this abnormal calcium response. And we looked at a large library of existing drugs, so ones used to treat other diseases and many of which you'd actually find in the pharmacy. It turns out that drugs that are used to treat diseases like hypertension or anti-arrhythmias or. anti-inflammatory drugs actually are able to fix this calcium response in schizophrenia.

Chris - How do know though, Santiago, that if you give that drug and it fixes it in a blood cell it's going to fix a brain cell?

Santiago - That's a very good question. In this study what we did was to compare the activity of the drugs in the blood cells with their activity in human nerve cells, so we see that the drugs actually work in nerve cells as well. As a follow up as well, we tested whether the cellular response was able to predict the response to clinical treatment in an independent patient cohort. So this this really opens up the way for using it for personalized medicine.

Katie - It sounds like the logic of using pre-existing drugs is that you're not having to make an entirely new drug which costs a lot of money and takes a lot of time?

Santiago - Absolutely. It's about using drugs which we know are safe in humans and it provides a means to bring them to the clinic in less time and at a lower cost.

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