Brain organoids developed by Jens Schwamborn are suitable for testing drugs against coronavirus
Neuroscientist Prof. Jens Schwamborn is actually working on Parkinson’s disease research with OrganoTherapeutics, a University of Luxembourg / Luxembourg Centre for Systems Biomedicine (LCSB) spin-off company he founded with colleague Javier Jarazo. Mini-brains developed in vitro will help understand how Parkinson’s attacks parts of the human brain. Furthermore, Jens Schwamborn can use them to test active substances that could potentially be used to combat Parkinson’s disease. But the brain organoid model can also provide valuable research results in the fight against SARS-CoV2, which was the reason for the Luxembourg government to support OrganoTherapeutics in a collaboration with the Luxembourg Institute of Health (LIH) and DeepBioInsights. Jens Schwamborn explains in detail what the research approach is all about:
– The brain organoid model
– How SARS-CoV2 might attack the human brain
– The brain organoid model approach to SARS-CoV2 research
– Research on SARS-CoV2 using mini-brains
– Drug repurposing – a possibility for drug discovery
THE BRAIN ORGANOID MODEL
For ethical reasons, research directly on the human midbrain is virtually impossible, and the transfer of experimental results from animal studies to humans may be limited. It was this circumstance that inspired Jens Schwamborn to use a new research model. For this purpose, skin cells are taken from people suffering from Parkinson’s disease, which can be treated with various substances and thus converted into stem cells. The stem cells obtained in this way can in turn be used to develop other cell types, such as neurons. This step is crucial for Parkinson’s research. Although it is not possible to recreate real, fully functional human brains in this way, adds Jens Schwamborn, the neurons obtained have many structural and functional similarities to a complete human brain. This makes them an ideal research and testing environment for neuron-attacking diseases like Parkinson’s.
HOW SARS-COV2 ATTACKS THE HUMAN BRAIN
Numerous studies of people suffering from SARS-CoV2 and autopsies of people who died from the coronavirus now provide a clearer picture of the virus‘ points of attack in the human organism. For Jens Schwamborn, these findings are an important starting point, because the examinations and autopsies confirmed that SARS-CoV2 possibly attacks the central nervous system and the human brain. Furthermore, it was found that the intestine can also be affected by SARS-CoV2. This is less relevant in terms of symptoms, but for Jens Schwamborn this finding is also important, as it shows that the virus is able to occupy certain types of cells and tissue and multiply there. SARS-CoV2 viruses have also been detected in the kidneys and livers of patients with the disease, affecting mainly patients with hypertension, heart disease and diabetes.
THE BRAIN ORGANOID MODEL APPROACH TO SARS-COV2 RESEARCH
The study results, which point to a neurological attack of SARS-CoV2 in the human organism, inspired Jens Schwamborn and his team at OrganoTherapeutics to modify their brain organoid model so that it can be used as an approach to research on SARS-CoV2 in the same way that it is already being used in the search for active agents against Parkinson’s disease. After infection with the virus, the neurological aspects of a SARS-CoV2 infection can be specifically investigated. For this, Jens Schwamborn has chosen to collaborate with the Luxembourg Institute of Health (LIH) and DeepBioInsights, which will allow OrganoTherapeutics scientists to expand their model for corona research.
RESEARCH ON SARS-COV2 USING MINI-BRAINS
The environment that OrganoTherapeutics‘ brain organoids represent resembles the human midbrain and is therefore particularly well suited for imaging infections with SARS-CoV2 here and developing an understanding of how the virus attacks neuronally, explains Jens Schwamborn. The experience he has already gained with OrganoTherapeutics through his research on Parkinson’s disease will benefit him in the generation of brain organoids. At the Luxembourg Institute of Health, the minibrains are infected with SARS-CoV2. Jens Schwamborn notes that LIH is predestined for this step because it has laboratories with an extremely high level of protection, which prevents the virus from spreading to scientists working on it. For this reason, SARS-CoV2 is inactivated with a treatment after infection of the brain organoids, which enables safe transport back to OrganoTherapeutics. There, Jens Schwamborn and his team are investigating the changes caused by the coronavirus in the brain organoids. High-throughput microscopes and powerful computer clusters are used here.
DRUG REPURPOSING – A POSSIBILITY FOR DRUG DISCOVERY
Jens Schwamborn has extended the original model for research with mini-brains to study SARS-CoV2 in brain organoids. The next step is to test whether drugs already known in other contexts might contain active ingredients that also prove effective against SARS-CoV2, thus making it possible to repurpose existing drugs. This is known as drug repurposing. To this end, Jens Schwamborn is cooperating with DeepBioInsights, which developed an approach in the field of artificial intelligence. In this way, DeepBioInsights can also name some molecules with regard to SARS-CoV2, which are possible candidates for active substances against the neuronal aspect of the coronavirus and can be tested on the brain organoids. These tests will again be performed by Jens Schwamborn in cooperation with the Luxembourg Institute of Health and the brain organoid models infected with SARS-CoV2. Then the efficacy of the tested compounds will be investigated and analyzed. As soon as compounds are found at this point that are effective against SARS-CoV2, not only can the drugs containing them be repurposed, but it may also be possible to develop new drugs from these compounds that specifically inhibit the neuronal attacks of SARS-CoV2, Jens Schwamborn concludes.
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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