Jens Schwamborn s brain organoids help in drug discovery for corona drugs
Neurobiologist Prof. Jens Schwamborn develops mini-brains. What initially sounds like a science fiction movie has long been reality in the research labs of OrganoTherapeutics, the company Jens Schwamborn founded with his colleague Javier Jarazo as an offshoot of the University of Luxembourg / Luxembourg Centre for Systems Biomedicine (LCSB) in 2019. Here, in vitro brain organoids, precisely those mini-brains, are developed from human stem cells, originally with the aim of helping to develop and research new effective drugs against Parkinson’s disease. As it turned out, however, the brain organoids can also make a valuable contribution in the fight against SARS-CoV2 by using them to represent a Covid 19 infection instead of Parkinson’s disease. In this way, the mini-brains can be used to study how SARS-CoV2 attacks the human brain and which active substances can help prevent this. This is one reason to ask Jens Schwamborn about his work in more detail:
– What exactly are brain organoids?
– How does SARS-CoV2 attack the human body?
– Why can the mini-brains support covid research?
– How are brain organoids used for SARS-Cov2 research?
– What is drug repurposing?
WHAT EXACTLY ARE BRAIN ORGANOIDS?
The focus of Jens Schwamborn’s research is to develop new therapies that can prevent disease-induced death of neurons and nerve fibers. In this way, the course of certain diseases could be slowed down or, ideally, even stopped altogether, which could significantly improve the quality of life of those affected. Jens Schwamborn’s idea is to start his research directly at the nerve cells. For this purpose, living skin cells are removed from patients, which is not a particularly painful or unpleasant procedure. OrganoTherapeutics’ main research is on Parkinson’s patients, which means that the removed skin cells carry the genetic information related to Parkinson’s disease. Although it is not possible to reconstruct a complete human brain in this way, Jens Schwamborn emphasizes, the stem cells can be used to develop nerve cells that are similar in structure to those found in a complete brain. These brain organoids can therefore be used to test whether and how certain active substances are able to prevent the damage that Parkinson’s causes in the nervous system.
HOW DOES SARS-COV2 ATTACK THE HUMAN BODY?
For active substances to be developed into drugs, the disease itself must first be understood, explains Jens Schwamborn. SARS-Cov2 infected individuals often show changes in the brain and nervous system, suggesting that covid can cause damage to the central nervous system and brain. Autopsies of people who died from SARS-CoV2 confirmed this. The intestines, kidneys, and liver are also often affected, usually not seriously in terms of symptoms, but showing that the virus is capable of infecting and replicating in certain types of cells and tissues. Especially patients with hypertension, heart disease and diabetes can be affected.
WHY CAN THE MINI-BRAINS SUPPORT COVID RESEARCH?
It is now considered proven that SARS-CoV2 also attacks the body neurologically. For Jens Schwamborn, this finding provided the link to his own research with OrganoTherapeutics – the brain organoids they have developed can start here and be used for research on SARS-CoV2 in the same way as for Parkinson’s research. In contrast to the tests for Parkinson’s disease, healthy skin cells must be removed and developed into healthy stem cells from which healthy mini-brains can be generated. These are finally infected with SARS-CoV2 and thus represent the events of a covid infection in the neurological area of the human body. Due to the urgency of this project, which is supported by the Luxembourg government, OrganoTherapeutics worked in close cooperation with the Luxembourg Institute of Health (LIH) and DeepBioInsights on this project.
HOW ARE BRAIN ORGANOIDS BEING USED IN THE FIGHT AGAINST SARS-COV2?
The mini-brains created in vitro by OrganoTherapeutics will be infected with SARS-CoV2 at the Luxembourg Insitute of Health. Jens Schwamborn notes that this step is being taken by LIH in particular because laboratories with a particularly high level of biological protection are required to handle SARS-CoV2 viruses, in order to prevent the virus from circulating unnecessarily and endangering people working on it. Therefore, after infection, the brain organoids will undergo a treatment that inactivates the virus in a way that prevents further spread with it and allows OrganoTherapeutics to continue research on the mini-brains, how SARS-CoV2 causes neuronal cell death and a reduction in neuronal function. High-throughput microscopes and powerful computer clusters will be used for this step, Jens Schwamborn reveals. The result will be to determine which genetic changes can be caused by infection with SARS-CoV2.
WHAT IS DRUG REPURPOSING?
OrganoTherapeutics has extended their original model for studying Parkinson’s disease with brain organoids for SARS-CoV2 research. An additional step is to test ways in which drugs that already exist for other diseases can be repurposed to treat SARS-CoV2. This is the case if they contain an active ingredient that can also be used against the covid virus. In such a case, where a drug originally developed for one disease can be effectively used against another disease, this is called drug repurposing. To test these possibilities, an approach that uses artificial intelligence is being used due to the abundance of drugs and compounds. DeepBioInsights is a company dedicated to this approach and is therefore an important cooperation partner of Jens Schwamborn and OrganoTherapeutics. The model developed by DeepBioInsights has already been successfully used, for example, in the search for active substances against Alzheimer’s disease. For Jens Schwamborn, this collaboration creates an ideal prerequisite for also being able to name some molecules on the brain organoid model in the short or medium term, which can then be used experimentally as active agents against SARS-CoV2. The artificial intelligence model provides drug candidates that are tested on the brain organoids and evaluated for their efficacy. Once suitable active substances have been identified, they can be repurposed for the treatment of SARS-CoV2 if necessary, explains Jens Schwamborn.
OrganoTherapeutics use cutting-edge human-specific mini-brains for the discovery and development of effective drug candidates targeting Parkinson”s disease. We screen new molecules on our proprietary human-specific minibrains which represent a model mimicking faithfully the human Parkinson”s disease pathology. OrganoTherapeutics aims at developing new drug candidates against Parkinson”s disease which are tested in state-of-the art 3D patient models. OrganoTherapeutics has developed first own proprietary drug candidates and has access to attractive libraries for further screening.
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