Dr. Hayder Amin and Dr. Caghan Kizil from the DZNE site in Dresden want to use the latest technology to accelerate the development of drugs against brain diseases.
To do this, they are generating an innovative technology platform called “i3D-Marker”, which is based on high-density microelectrode arrays and 3-dimensional networks of human neurons. Connections to be tested are dripped onto this structure and the reaction of the neurons is determined using artificial intelligence.
With this platform, the DZNE scientists want to optimize the selection of robust drug candidates for clinical studies and help to avoid dead ends in the development pipeline. The validation of this approach is funded with 820,000 euros from the “Helmholtz Validation Fund”. Additional financing is provided by the DZNE, bringing the total budget to around 1.2 million euros. The aim of the researchers is to commercialize this new technology and prepare it for industrial use.
Drug development is costly and characterized by setbacks. “In recent years, most of the new drugs for brain disease have failed in human studies. One reason for this is the inefficient in vitro assays for neurological diseases – especially in the early phase of drug development before clinical trials begin, ”says Dr. Caghan Kizil. , a neuroscientist focused on developing experimental models and new understandings of Alzheimer’s disease.
His colleague from Dresden, Dr. Hayder Amin noted, “The existing methodology is a fundamental flaw. The human brain is enormously complex and cannot be adequately modeled in the laboratory using current methods. You are too reductionist to see the real effects of a drug on neural networks. In particular, two-dimensional cell cultures and conventional data acquisition methods fail to capture the complex electrophysiological and cellular properties of the brain. “Amin, who has extensive expertise in experimental neuroscience and multilevel neurotechnology and the development of computational tools to study neuronal dynamics, added:” This creates a critical need for tools that better support the development of new drugs. “
A fusion of technologies
The Dresden researchers have innovative ideas to tackle this problem. “i3D-Markers”, their innovative technology platform, could answer a critical question in drug development: “How would a certain drug candidate influence the human brain networks: good or bad?” Experience shows that this question is difficult to answer before human clinical trials.
In fact, many drug candidates that show medical potential in laboratory or animal experiments fail in clinical studies due to undesirable effects on the human brain. The DZNE scientists are optimistic that i3D markers can make a difference. “
Dr. Hayder Amin, ZNE – German Center for Neurogenerative Diseases
“Our goal is to validate that our technology can predict better than current methods whether an experimental drug has the intended effect on humans. Hopefully this will help accelerate the path to new drugs, avoid dead ends in drug development and reduce development costs, “said Kizil.
The concept of the Dresden researchers fuses neuroelectronics with an innovative cell culture method. “I3D-Markers uses neural cultures connected to a microchip. We grow neurons on high-density microelectrode-based chips to form a 3D neural configuration like in the brain. This setup enables us to track the electrical activity of thousands of neurons simultaneously with high spatiotemporal resolution, “explained Amin.” This large array of tiny sensors gives us insights into the dynamics of this very complex human neural network.
A drug to be tested is dripped onto the neurons in a specific concentration. “Then you start recording electrophysiological data that is collected by our sensors,” said Kizil.
Intelligent prediction algorithms
Although the network will contain more than a hundred thousand neurons, this cell culture, including the microchip, would fit on an area ten times smaller than a 2 euro cent coin. However, the information about neural activity will be complex as it is represented by thousands of microcontact sensors. The scientists will therefore use artificial intelligence methods for the analysis.
Such algorithms identify and extract patterns from complex multidimensional data. “By using artificial intelligence and special mathematical approaches, we want to develop so-called functional biomarkers based on neural network activity. These biomarkers will tell us whether the network is doing well or not, and whether a particular drug is affecting that condition, will help us identify promising compounds, “said Amin.
Strive for a start-up
The DZNE scientists are not starting from scratch: They have a proof-of-concept from previous studies that shows that the various technologies included in this project can actually be successfully merged. On this basis, the validation process that is now starting is to develop a technological platform that can ultimately be commercialized.
A scientific advisory board and several doctoral students will be involved. In addition, industrial partners from the fields of microtechnology and drug manufacturing will provide in-kind contributions. “Our goal is to build a fully functional prototype and test it within the next two years,” said Amin. “When the technology is ready for routine use, we would first look after external customers internally. This can be research institutes and pharmaceutical companies. In the long term, we aim to found a start-up company. “
Source:
ZNE – German Center for Neurodegenerative Diseases
