Breakthrough promises more effective drugs

Chinese researchers have devised a new method for designing drugs that target multiple aspects of complex diseases, potentially offering a breakthrough for treating mental illnesses like schizophrenia and dementia.

The method, called the flexible scaffold-based cheminformatics approach, creates drug molecules with a deformable structure that can bind to different parts of a cell receptor in various shapes. This allows the drug to address multiple aspects of the disease simultaneously.

A study detailing the approach, a collaboration between researchers in structural biology, cellular function, behavioral pharmacology and cheminformatics — the use of information technology to understand problems in chemistry — was published on Thursday in the journal Cell.

Mental illnesses are notoriously complex, with symptoms ranging from hallucinations and mania to social withdrawal, memory loss and insomnia. Traditional single-target drugs often struggle to address the full scope of such conditions.

“It’s widely acknowledged that for complex mental illnesses, drugs targeting multiple aspects are more effective than those targeting just one,” said Wang Sheng, a corresponding author of the study and researcher at the Chinese Academy of Sciences’ Shanghai-based Center for Excellence in Molecular Cell Science. “This can not only improve efficacy but also alleviate more symptoms.”

The new approach offers several potential benefits for patients. By targeting multiple aspects of the disease, such drugs could potentially reduce the number of medications needed, simplifying treatment regimens and improving adherence. Additionally, the multi-target approach could minimize side effects often caused by interactions between multiple medications.

The researchers designed a molecule called IHCH-7179 using the new method. It can interact with two different receptors for the neurotransmitter serotonin. Depending on its shape, IHCH-7179 can either inhibit or activate the receptors, potentially suppressing manic and hallucinatory symptoms while also improving cognitive function.

Animal studies showed promise, with the new compound alleviating symptoms like mania and hearing impairment in models of schizophrenia and dementia.

“Our compound, compared to existing drugs with a single effect, could offer additional benefits like slowing cognitive decline,” Wang said.

The researchers believe the method also has broader implications for future drug development.

“The human body’s major systems are complex and interconnected,” said Xu Huaqiang, a co-corresponding author and researcher at the Shanghai Institute of Materia Medica. “This approach suggests a future direction for drug design that considers a disease’s impact on multiple systems.

“It could be significant for developing drugs targeting immunity, metabolism and other areas.”

Clinical trials for a schizophrenia treatment based on the method are expected to begin later this year, offering a potential new weapon in the fight against complex mental illnesses.