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Can SARS-COV-2 access the brain and cause neurodegeneration?

April 28, 2020

Dr. Tony Wyss-Coray is a Professor of Neurology at Stanford University, where he studies the role of immune responses in ageing and neurodegeneration. The Wyss-Coray lab has been at the forefront of fascinating findings in the area of neurodegenerative diseases, memory, and immune function. Tony and his team of 25 researchers discovered that the transfusion of blood from young to old mice rejuvenates the latter’s ageing brain. Blood transfusion shows promise as an anti-ageing therapy for humans, currently undergoing clinical trials. FORM's Founding Partner Markus Okumus Zoomed in with Tony to talk about the current COVID-19 crisis, the effect of viral infections on the brain, and how to combat ageing more broadly.

Markus: Tony, thank you very much for being with us today. You’ve had a long and outstanding career as a research scientist. Do you mind telling us a little bit about your work and maybe some of the discoveries you’ve made? 

Tony: First of all, thank you very much for having me. It’s a real pleasure to be here. I’ve been very fortunate to work with an outstanding team of young scientists who discovered that the brain, which is the main focus of our research, seems to be susceptible to factors that are present in the blood. As we age and the brain becomes more prone to neurodegenerative diseases, it also seems to respond to factors, specifically proteins, that we’ve identified in the blood. For example, we’ve shown that if you treat an old mouse with blood from a young mouse, you can actually regenerate its brain and make it function more like a younger brain. And that really has spawned a new wave of research and experiments to try to understand how this all works. 

Markus: That’s fascinating, and I’m interested to hear about the connection between that and COVID-19 treatments later. Well, speaking of COVID-19, I wonder how the current pandemic has affected your own life and work. Now that you’re probably out of the lab, what does a normal day look like for you? 

Tony: You know, it’s funny. We just moved into a new building, probably one of the most beautiful buildings on campus here at Stanford. As soon as the last groups moved in, we received a mandate from the county that we should stay at home, and so the building shut down. Initially, I was quite anxious to try to keep the lab going. We have about 25 scientists, and the majority of them work at the bench, meaning they do experiments and some of them work with animals. So for the majority of people, it meant the end of their experimental work, and that’s been a struggle. What I try to do is have regular meetings, at least once a day. We usually have a morning meeting where people from the lab take turns presenting. We’re trying to do literature reviews and review publications since lab work has slowed down significantly. We usually have 30 people who Zoom in and participate, and we do have discussions but I feel they’re usually limited, very different from being in the same room together. 

Markus: How has the abrupt end of lab work affected your research team?

Tony: Well, the good thing is that we were able to finish experiments that involve animals and that required us to take measurements or harvest organs. But other than that, we weren’t able to finish much else. At the start of the crisis, I was actually busier than my usual schedule, since I was trying to organize everything. Right now, things have eased off a bit, but we’re still working on multiple reviews and manuscripts, so that keeps me busy. But I still worry about my staff sometimes. Many of them are young and live alone, or maybe with another person. And so they run out of work and have nothing to do, so it can be really tough for them. But on the other hand, it seems that we can start going back to work pretty soon. We’re actually working on a project related to COVID-19, where we’re trying to understand how the virus affects the nervous system and eventually enters the brain. We have a few people working on that and they’re actually back in the lab. So it doesn’t look all that bad after all. 

Markus: Interesting. We’ll definitely get back to your project on COVID-19. But what I wanted to ask you first is what surprises you most about how the crisis unfolded and continues to unfold today. Was there anything specific that caught your attention? 

Tony: What really surprised me is how societies with different political systems came together and decided to severely restrict economic activities to save lives. I think that’s a very positive thing. I did not expect that people would be willing to do this, that they would listen to the epidemiologists and implement pretty severe restrictions on normal life. On the other hand, it also brought out some of the differences in contrasting forms of government, with more autocratic governments deciding and acting in a top-down approach while democratic societies place every major decision under debate and scrutiny. Unfortunately, in the United States the whole thing has become a political issue. We have presidential elections coming up, and so everything is calculated in terms of political positioning for the upcoming elections. 

Markus: Right. Well, on a more positive note, do you think the pandemic has changed the standing and importance of scientists for politicians and the economy more broadly?

Tony: I believe so. But let’s remember again that there are different types of societies. I think in the US, for example, science has become just another way of looking at things, not the objective truth-bearer that sensible people think it should be. I think this epidemic revealed to people that there are facts in the world, not just opinions, and that science plays a role in identifying these truths. I do think, overall, people realized we need science to understand and solve the world’s problems. I believe this will have a longer-term effect on global society, and I personally hope that it will translate to climate science as well. 

Markus: Obviously, we’re seeing how important cross-border research collaborations are. Do you think the current crisis will have an impact on global scientific collaboration in the future? 

Tony: Well, it’s hard to predict. We’re seeing scientists working together across the globe to better understand the virus. There’s never really been a time where people have worked so closely together across borders. People are doing experiments and immediately posting them online, a trend that has accelerated during the crisis. So scientists really do want to collaborate across borders, but then you have other things that come in and muddle the picture. For example, you have global politics and international relations, which significantly impact the way science is conducted between countries. You also have societal trends that come into play. For example, in the US at least, there are many isolationists who want the country to keep to itself and cut down foreign relations as much as possible. So I don’t know if the scientific community will quickly open up to China after all this is over. It’s possible, but then again, people might say that the virus came from China and that scientists in the West should stop working with Chinese researchers as a result. 

Markus: Throughout your career, you’ve looked at neurodegeneration and amnesia-related diseases like Alzheimer’s. I’m wondering if people with neurodegenerative diseases have a higher likelihood of being negatively impacted by viral infections like COVID-19. So far, we know that the main risk group consists of older people, and people with certain pre-existing conditions like heart disease. But we’ve heard little about people with neurodegenerative diseases. Is there any evidence to believe that these people are in the risk group as well?

Tony: We only recently started studying the immune system in patients with Alzheimer’s and Parkinson’s disease, and it has become possible over the last few years to get a very “high resolution” on the immune system and start to understand what individual immune cells recognize. And that led us to discover immune cells, called T lymphocytes, in the brains of patients with neurodegenerative diseases. Now the interesting thing is that these cells recognize viruses, but only those that have been around for hundreds of years, such as the Epstein-Barr virus or other herpes viruses. And this could be relevant for COVID-19, since we know that the virus can affect cells in the brain. There’s a lot of neurological symptoms that accompany COVID-19 and thus indicate that the virus has access to the brain. Some of these symptoms include paralysis, loss of smell and taste, etc. So this has led to the question of whether the virus can have long-term neurological consequences, and even promote neurodegeneration or have effects on people with pre-existing neurodegenerative diseases. 

Markus: Very interesting. Well, to broaden up the discussion a little bit, let’s talk about preventive measures against viral infections. You’ve looked at immune responses in ageing and neurodegeneration. Do you have any advice to people who want to build stronger immune systems to protect themselves from the severe effects of viral infections? 

Tony: At this point, drugs are not available yet that have noticeable effects on ageing. And I think it’s too early to know if young blood or young plasma, the proteins in the blood, will be beneficial for humans, although we’re currently conducting clinical trials and we should have an answer in the not so distant future. But what we see over and over again is that some of the same effects that we can produce with young plasma, you can achieve with exercise or fasting, specifically intermittent fasting where you have a very long period before you eat your next meal. That forces your body to enter into a different type of metabolism that seems to be beneficial for the immune system. So it’s mostly lifestyle interventions like healthy eating, exercise, and fasting that are going to help us both stay healthy in the long run and protect us from the adverse effects of viral infections. 

Markus: And do you follow these types of interventions in your private life, or perhaps with your family?

Tony: I definitely eat healthy. We even have a small garden and we try to eat fresh and organic food. I try to get my exercise every week. Fasting? Well, not as much. I’ve done it a few times, and it’s a bit more challenging to be honest.  

Markus: It is! Earlier we were talking about your work on possibly using blood to reverse ageing. Now whether through blood or medication, when do you think we will see anti-ageing treatments available to people? Are they 5, 10, 30 years out? 

Tony: I think we will start seeing treatments that target ageing rather than individual diseases over the coming 5 to 10 years. They won’t necessarily make us live longer or have very profound effects, but I think they’ll start to chip away at some of these age-related diseases. As you know, many of the major diseases that affect society are affecting older people. At age 70 or 80, a lot of people have two or three major diseases - heart disease, arthritis, cognitive problems or even dementia. And if you would slow down ageing, you would have an impact on all these diseases. So to me, it’s clear that this is the direction that medicine, pharma, and healthcare have to aim for in order to have a serious health impact on our society.

Markus: Well, your answer there just got me thinking. Would you say ageing is a disease?

Tony: I wouldn’t say it’s a disease, but a foundation of most of the major diseases that we haven’t been able to tackle yet. In the context of COVID-19, it’s really interesting that this is a virus that’s remarkably selective for older people. For example, flu affects everybody, including children and young people. But COVID seems to really be affecting older people and taking advantage of an ageing immune system - not necessarily a diseased one.

Markus: So the study of older people with ageing immune systems does offer insight into something as common as a virus.

Tony: Absolutely. I think that our study of older organisms helps us understand why we become susceptible to ageing-related diseases more broadly. Even if you look at the composition of the blood, it changes dramatically as people get older. It’s just a reflection of how the body is very different when it’s old compared to when it’s young, and that probably makes it susceptible to certain diseases. In this case, to a virus that obviously has taken advantage of that fact. 

Markus: On a more positive note, what are your hopes in relation to the current crisis? What are some of the positive outcomes we might witness once things normalize?

Tony: Well, as I said earlier, I’ve really been inspired by the global approach to combat the virus - it hasn’t been perfect, of course, but what’s been especially fascinating is the quick global information exchange among scientists. I really hope that this global approach to solving important problems will continue after things come back to normal. Also, I’ve observed that people are more willing to ask for and follow the advice of health experts and government officials. I believe this to be a positive development and hope it continues after the crisis as well. We’re also seeing governments, experts, and even people planning ahead more so than before. It looks like there’s been a stronger shift toward the idea of preventive health. To me, the question at this point is, are we going to use this model for other types of diseases and focus on prevention rather than treatment? Or is the focus on preventive health only a one-off isolated phenomenon specific to COVID-19?

Markus: Well let me ask you then. Do you think medical and health research will shift toward prevention?

Tony: I hope so. COVID-19 is just one example of research focusing on prevention. You know, in the context of vaccination, for example, there’s been a growing movement of people who say we don’t need vaccines, that they’re dangerous, etc. This pandemic clearly shows that without a vaccine, we won’t be able to overcome this challenge. The virus will come back on a regular basis unless we have a vaccine that can protect us. So I hope that research will start paying more attention to prevention for a diverse range of diseases. 

Markus: What’s your estimation of when we’ll have a vaccine?

Tony: I’m not an expert in this, so I really can’t say when. But I will say this. It’s not easy to test vaccines. If you test a vaccine simply by waiting for people to get exposed to the virus and see if they’re protected by the vaccine, you rely on the virus infecting people naturally, which is a rare occurrence given social distancing measures. If we were testing an influenza vaccine, we would quickly know if the vaccinated people are protected since influenza affects a large number of people every year. But if it’s a virus that only infects 1% of the population because of social distancing measures, you will never find out if vaccinated volunteers are protected against it. The solution to this is to have people inoculated with the virus after getting the vaccine, which is a very difficult type of clinical trial, with its own risks and limitations. 

Markus: I see. Two more questions and I will let you go, Tony. You know about all the preventive measures out there to protect ourselves from getting infected - social distancing, washing hands, etc. What do you personally recommend people to do, whether it’s washing hands or something entirely different? 

Tony: I think old people should protect themselves as much as possible and avoid exposing themselves to any situation where they may get in contact with the virus.  They should avoid contact with people without wearing a mask and gloves. But on the other hand, I believe that we need to reopen our society and get back to normal, and I think younger people need less protection. In the end, it’s the monitoring that will tell us whether the virus is spreading again and if we have to tighten up our measures. Ultimately, it’s only a vaccine that will allow us to get back to normal society. 

Markus: My last question, Tony. You’ve had an outstanding research career. If you were to give 20 year old Tony some advice based on your experience and knowledge, what would it be?

Tony: Follow your passion, be excited, get out into the world and do what you love. It’s not complicated or original, but hey, it’s true.

Markus: Thank you, Tony. It was great talking to you.

Tony: Thank you, Markus! 

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