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The long-term work of the Austrian geneticist Josef Penninger on the enzyme ACE2 could bring a breakthrough in the treatment of the new corona virus. An active ingredient from the Viennese biotechnology company Apeiron will soon be tested in China – Penninger is on board. In the conversation, Penninger warned against underestimating the virus.
The SARS-CoV-2 virus – like its close relative, the SARS virus that appeared in 2002 – uses the ACE2 receptor to get into human cells. The 55-year-old from Upper Austria and his team came up with the idea a few years ago to use biotechnologically produced human angiotensin converting enzyme 2 (rhACE2) in therapy for lung failure.
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The Apeiron co-founder and former head of the Institute for Molecular Biotechnology (IMBA) of the Academy of Sciences (ÖAW), who is now active in Canada, subsequently developed the drug candidate under the name “APN01”. On Monday evening Penninger spoke at an event organized by the Austrian-American Society on “The Corona Virus – First Successes in Drug Development?” In Vienna.
APA: There is a lot of speculation about the new corona virus. How do you currently assess the danger?
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JOSEF PENNINGER
Josef Penninger was born on September 5, 1964 in Gurten in Upper Austria. He completed his medical studies at the University of Innsbruck, where he completed his doctoral thesis in 1990. He moved to Canada as a post-doc and subsequently rose to become a renowned scientist. In 2002 he took over the newly founded IMBA in Vienna, which under his leadership became an internationally renowned research institute. Penninger has headed the Life Sciences Institute (LSI) at the University of British Columbia in Vancouver (Canada) since the end of 2018, but still runs a laboratory at the IMBA.
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PENNINGER: We should not underestimate this visual acuity because the lethality that the WHO announced last week is thirty times higher than that of the ‘normal’ flu virus. If the corona virus really infects as many people as some predict – similar to the flu virus – then we have a problem. In the end you are always wiser whether you have overreacted. But I think it’s better if we overreact. We know it affects us. We already have a number of cases in Austria and Vienna.
You have also worked intensively on the previous virus – SARS. Are you surprised by the dynamics of the current spread?
Yes, because the SARS virus was not very contagious. You had to be seriously ill to infect someone. This allowed the chain of infection to be checked relatively quickly. The new virus is very contagious, probably more contagious than the flu, because even people with no or very mild symptoms can carry the virus. Even with the best will, this makes control difficult. In China it was successful, but in our society it is rather difficult.
You are in contact with Chinese researchers and doctors. Have you personally been able to get an idea of the situation there?
No, I actually wanted to go this week, but there is no flight anymore.
What role has the ACE2 enzyme that you have researched in recent years and developed into a drug in the disease?
It has two roles: First of all, ACE2 is the door through which the virus has to pass in order to infect us. Our protein, the biotechnologically produced, recombinant, soluble ACE2, looks just like the door and intercepts the virus so that it does not find the right entry. It blocks the virus from entering our cells.
Second, it protects against lung failure. One reason why the SARS virus was so deadly is that it bound to the cell surface at ACE2, and the two then went together into the cell, where the virus multiplied. As a result, ACE2 was missing and protection against lung failure was reduced. In a nutshell: our active ingredient dampens the infection and protects our lungs from failure. This is the data that we and other researchers currently have.
Is the planned study on 24 seriously ill people in China already underway?
We actually wanted to start last week, but the Chinese government decided that there should be no small, local pilot studies. The activities are only controlled centrally – which also makes absolute sense. We are currently looking for a larger, definitive study that may be a bit delayed but will give us much more information. We will then definitely know whether it will work or not. If everything goes well, we will do a large clinical trial in three or four weeks. In the end, we may be even faster than originally planned.
Are there ideas for similar tests in Italy or even in Austria?
We are also actively talking to doctors in Italy and Switzerland. When we started planning, the rapid spread to Europe was not yet foreseeable.
What results do you hope for from the now larger study?
Penninger: We hope that the virus will be reduced and that people with serious illnesses will not slide into the very difficult stage – that they can be stabilized. But we all know that there are no miracle cures. So drugs are also needed that can really help sick people.
Also apart from your approach: how far are you in drug development at the moment?
Penninger: Many, many companies are currently trying to develop vaccines. We are talking about one and a half to two years, because this has to be tested very carefully in humans so as not to worsen the disease with the vaccine.
Another important approach is that companies are also using artificial intelligence methods to find substances that prevent the virus from multiplying. That makes sense, but such drugs can also promote viral resistance. The breakthrough in HIV has brought about attacking three or four aspects of the virus. We have to get there too.
Our approach is to lock the door and stop letting the virus in. It’s also about reducing inflammation in organ failure. So there are many approaches and I was pleasantly surprised at how quickly the world of science reacted to this outbreak. Biotechnology has just accelerated insanely and of course that gives hope!
What does it mean for you as a scientist and entrepreneur when something starts small in your own laboratory and then possibly has such a large impact for many people? That is not everyday.
Not really. We found ACE2 in 2000 and found out how it actually works. We started working on lung failure long before the SARS virus. Then we did this now classic work on ACE2 being the essential receptor for the SARS virus. In 2005 we were able to show in the journal “Nature Medicine” that ACE2 also protects against lung failure. Everyone quotes this work today, also in connection with the new outbreak. I think that’s a good argument for basic research! Sometimes you have to research things that may not really become relevant until 15 years from now.
It is astonishing that scientists from China, North America, Europe and Apeiron have come together in a very short time to further develop the drug. We know that this is the logical approach and that it is safe. In careful studies, we now have to test whether it really works. It was really a team effort.
Nikolaus Täuber (APA) spoke with JOSEF PENNINGER
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