- A novel technique has been developed that can be used for screening potential new psychiatric drugs
- Human blood cells are used for screening the new drug molecules
- This could lead to the development of personalized therapies for neuropsychiatric disorders
New approach to
drug discovery developed by scientists at the University of Cambridge, UK,
could lead to personalized medicines for treating neuropsychiatric disorders,
reports a new study published in Science Advances, a publication of
the American Association for the Advancement of Science (AAAS).
The study used live blood cells from patients suffering from mental illnesses to identify potential targets for drug discovery research. Importantly, this research has the potential for substantially accelerating the search for new drugs for treating psychiatric disorders such as schizophrenia.
The study was led by Professor Sabine Bahn, MD, PhD, MRCPsych, FRSB, who is the Laboratory Head at the Cambridge Center for Neuropsychiatric Research, University of Cambridge, UK. She also holds joint appointments at the Department of Chemical Engineering and Biotechnology at Cambridge and Erasmus Medical Center, Rotterdam, Netherlands.
Why is Drug Discovery for Mental Disorders Difficult?Mental illness accounts for 31 percent of total years lived with disability, which is the highest for all diseases across the world. Despite increased understanding of the biology of mental disorders over the years, no new drugs or improved therapies have been developed over the past several decades. In fact, most of the drugs that have been discovered so far have been due to sheer luck. This primarily stems from the fact that brain tissue samples cannot be collected in the same way as for other organs of the body, where biopsy samples are easily obtained for diagnosing, for example, cancer. Therefore, scientists have no idea what to target while developing new neuropsychiatric drugs.
What is Unique about New Technology?The uniqueness of the new technology developed by the Cambridge scientists arises from the fact that human blood cells share the same receptors and proteins that are present in the central nervous system (CNS; consisting of the brain and spinal cord), which are implicated in neuropsychiatric disorders. This is corroborated by previous studies which have shown that blood cells are linked to how the CNS functions. For example, bacterial infections of the blood often produce depressive-like symptoms in susceptible individuals.
This highlights the importance of using blood cells for testing new drugs. Importantly, there is substantial evidence that using primary cells from patients for drug testing can lead to higher success rates for drug discovery efforts.
"Psychiatric disorders are increasingly recognized as disorders of the whole body," said Bahn. She added: "This study proposes a shift in the field to directly explore live cellular function as a model for the disease."
How Were the Drug Candidates Screened?The potential new neuropsychiatric drugs were tested using a new technology developed by the Cambridge scientists, which is known as high-content single-cell screening. This technology was used for screening thousands of potential new drugs on blood cells obtained from 42 schizophrenia patients.
The research team also tested conventional psychiatric drugs on the blood cells of patients to see how effective the drugs were on those patients. The blood cells were analyzed before and after treatment with the drugs. The findings helped them to understand why some patients don't always respond to first-line therapies.
Importantly, the researchers confirmed that the blood cells did indeed share common receptors with the CNS by testing the new potential drug molecules on human nerve cells.
What are the Advantages of Drug Repurposing?The research team also tried to repurpose existing drugs so that they could be used for treating psychiatric disorders. Interestingly, drug repurposing can reduce the time and cost of bringing a new drug for clinical use by up to tenfold. Since drug development costs USD 2-3 billion over a span of 12 years, drug repurposing presents an effective alternative to bringing new treatments to patients at a fraction of the cost within a considerably lesser timeframe. This will also substantially reduce the need for animal testing, which is an added advantage.
Concluding RemarksThe lead author of the study, Lago concludes saying, "This is the most in-depth, functional exploration of primary psychiatric patient tissue to date and has the potential to substantially accelerate drug discovery and personalized medicine for neuropsychiatric disorders and other human diseases."
Funding SourceThe research was funded by the European Union (EU), the Engineering and Physical Sciences Research Council (EPSRC), UK, and the Stanley Medical Research Institute, USA.
- Drug Discovery for Psychiatric Disorders Using High-Content Single-Cell Screening of Signaling Network Responses ex vivo - (https://advances.sciencemag.org/content/5/5/eaau9093)