Israeli scientists fuse ‘brain tissue’ and electronic chips to test autism treatment
Biotech startup uses AI analysis of a ‘brain-on-a-chip’ made from stem cells to predict drug efficacy for neuropsychiatric disorders, expedite testing and development
Israeli entrepreneur and investor Shmulik Bezalel has traveled the world and donated funds for research to find a treatment for his son Itay who has low-functioning autism spectrum disorder. Itay is one of 254 million children and adults worldwide struggling with neuropsychiatric disorders without a suitable treatment.
Recognizing the limited therapeutic options for neuropsychiatric disorders, Bezalel teamed up with serial entrepreneur Boaz Goldman and neuroscientist Dr. Nisim Perets, and in 2021 founded an Israeli biotech startup with the vision to generate a simulation of the brain and test the efficacy of drugs.
That startup, Itay & Beyond — named after Bezalel’s child Itay — is now developing a drug discovery and testing platform for psychiatric and neurological disorders such as autism, epilepsy and schizophrenia.
“The vision was to establish a system that will test how a specific drug would influence Itay’s ability to learn, improve memory, or be more social,” Perets told The Times of Israel. “The goal is to create a system to predict the efficacy of specific drugs on the functioning of cognitive and behavioral aspects.”
In what sounds like something straight out of science fiction, the Israeli scientists led by Perets have been working at a lab at Jerusalem’s Hadassah Medical Center developing human brain-on-chip technology with a simulation of behavioral output.
In the lab, Perets and his team grew brain organoids — tissue that resembles parts of the human brain — in a petri dish from a single cell extracted from urine samples of patients with autism and epilepsy, which was then reprogrammed into a stem cell.
The lab-grown brain tissue is transferred onto an electronic chip, which is connected to a computer. The tissue sits on a multi-electrode array and each electrode records and can provide stimuli to the brain organoids. As such, brain-on-chip technology provides the ability to measure electronic signals from living brain tissue grown in vitro.
“We look at the brain as a computational machine — like a computer, and not as an organ like the heart or the liver,” said Perets. “The core technology we developed, the claim to fame of our company, is that we decided to gamble on putting brain organoids on a chip, so that we could record and stimulate the electrical activity of the brain and not just the molecules.”
“Using advanced AI technology and big data analysis, we can measure, study and provide insights into how brain organoids encode information and respond to stimuli, including different drug molecules,” he added.
Perets, who holds a PhD in neuroscience from Tel Aviv University and a post-doctorate from Haifa’s Technion-Israel Institute of Technology, said that neural coding, or how the brain works and encodes information, is key to understanding what “goes wrong in the brain” of patients with psychiatric and neurological disorders such as Alzheimer’s, epilepsy, Parkinson’s and schizophrenia.
Perets explained that once there is an interaction between the computer and the chip, the system can teach the cortical brain organoids simple tasks such as playing video games through a method called reinforcement learning.
“At the end of each video game we get a score. We then analyze it against the scores of other brain tissues that derived from healthy patients and those with disorders such as autism, or epilepsy, and search for drugs that can improve them,” said Perets.
The platform Itay & Beyond is developing aims to break a major deadlock in the development of drugs for patients with neuropsychiatric disorders, such as epilepsy, autism, dementia (including Alzheimer’s) and schizophrenia. When developing drugs, researchers try them out first on mice or rats and only then, if successful, on humans.
However, due to the significant differences between mice and human brains, these drugs often fail in human clinical trials, wasting years of costly development, Perets noted. Over the past two decades, only five new drugs were approved for neuropsychiatric disorders like autism and epilepsy, he said.
“One of the reasons that it is very difficult to develop drugs for neurological or psychiatric disorders is a poor efficacy prediction,” said Perets. “Most of the drugs tested on mice and rats have been found to be safe for humans, but to test the efficacy, it doesn’t extrapolate very well from mice to humans.”
In addition, the efficacy of new drugs is often validated only after phase 2 or phase 3 clinical trials, which can take 10 years and is very costly, he said.
Perets acknowledged that other scientists around the world are working to develop brain-on-chip models to better understand brain disorders and develop new drugs but, he says, most of the focus has been on safety and not efficacy, “because it’s a much lower-hanging fruit.”
Itay & Beyond’s platform is geared to help pharma companies predict the efficacy of drugs based on human brain organoids to help them make decisions about pre-clinical testing as well as develop new drugs or treatments that could treat patients successfully.
The system is still in its infancy, but Perets said that the biotech startup already has partnerships with small pharma companies in Israel and Europe that use its technology as a decision support system as to whether they should advance clinical trials for drugs.
Perets said the startup is on the cusp of publishing its first peer-reviewed scientific paper together with Hadassah Medical Center. For the coming year, Perets and his team are continuing to work on retrospective and prospective clinical validation of the technology platform, which will also include patient testing at Schneider Children’s Medical Center in Petah Tikva.
“Our main goal is to bring a new generation of drug testing methods to the world so that patients would not become the guinea pig, and to save money and frustration involved in trial and error,” said Perets. “The vision eventually is to have our own proprietary drugs for disorders like autism, epilepsy, and schizophrenia validated on our technology and sell them to pharma companies.” PJC
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