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
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,
The lead author of
the study was Dr. Santiago Lago, PhD, who is a postdoctoral scientist in Bahn's
lab. He developed the new high-content single-cell screening technology with
Dr. Jakub Tomasik, PhD, who is also a postdoctoral scientist in the same lab.
Why is Drug Discovery for Mental Disorders
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?
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.
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
How Were the Drug Candidates Screened?
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.
The 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."
The research was
funded by the European Union (EU), the Engineering and Physical Sciences
Research Council (EPSRC), UK, and the Stanley Medical Research Institute, USA. References :
- 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)