Neurological protein may hold the key for new treatments for depression, addiction and stroke

New peptide drug therapies offer the promise of effective treatments with fewer side effects.

Dr. Fang Liu

Senior Scientist, Department of Neuroscience, Centre for Addiction and Mental Health, University of Toronto
Professor Department of Psychiatry, University of Toronto

Associates and partners

Klara Vichnevetski, PhD
- Manager, Research Commercialization, Centre for Addiction and Mental Health, University of Toronto.

Issue

Traditional drug therapies for diseases like depression, addiction and stroke focus on shutting down receptors located on neuron cell membranes in the brain. This can provide an effective treatment in some patients, but can also cause unwanted side effects.

Why? Receptors are proteins located on neuron cell membranes in the human brain. Each receptor may have several functions. When traditional drug therapies shut down a receptor, it may disrupt more than the desired function – leading to side effects.

The challenge is to identify new drug therapies that can focus on the precise pathways between the specific receptors associated with disease – and delivery mechanisms that work with the new drugs.

Research

Award-winning scientist, Dr. Fang Liu, took up this challenge. Her team's receptor-receptor interaction research was sparked by a study of autopsied human brains from people previously diagnosed with major depression. Her findings showed that the coupling between two dopamine receptors was significantly enhanced in these brains.

In a novel approach, she generated a protein peptide to disrupt the binding of the two receptors, and discovered that, in animal testing, the new peptide therapy was very effective.

Dr. Liu and her team believe that protein peptides can form the basis for significant new treatments for many diseases. Her strategy is to develop peptide-based drugs and delivery systems with higher efficacy and fewer side effects. With the help of grants from CIHR's Proof of Principle (POP) program, she is pursuing three research projects: focusing on depression, addiction and Ischemic stroke. While each project targets a different disease, the combined learnings about the value of protein peptide therapies are paying off.

"The objective of all three POP projects is to test and optimize the peptides we have developed for depression, addiction and Ischemic stroke," said Dr. Liu. "Our critical challenge now is to identify a delivery method. Peptide molecules are larger than those used in traditional drugs and are easily digested. So our peptides can't be used in pill form. We are working to find and test new, non-invasive delivery methods."

Departing from traditional oral drug delivery has commercialization challenges. "Big pharmaceutical companies are comfortable with developing oral drugs. It's a tried and true pathway," explained Dr. Liu. "We're actively seeking partnerships with companies who want to explore novel and potentially very fruitful delivery approaches. The possibilities are very exciting, and I'm looking forward to revealing more about our unique delivery approaches as our partnerships develop."

Results

Confidence in the potential of the peptide therapy approach is high. Dr. Liu and her team are now sharpening their focus on the delivery mechanisms that can lead to viable commercialization.

"We are currently collaborating with a biotech company that specializes in drug delivery methods," said Dr. Liu. We're starting with the depression peptide, but we believe the mechanism can be applied to different peptides and treat different diseases. And we are conducting animal testing on delivery of the stroke peptide through an intravenous injection system. At the same time, we're also testing the side effects of our addiction peptide. The animal models show no side effects on learning, memory or movement, so we are very encouraged."

Looking ahead, Dr. Liu sees a bright future for peptide therapies. "We're building research and commercialization capacity with these POP projects. Our work is very novel. All the people trained in my lab are learning new techniques that they can put to use in their own careers. Over the past five years I've worked with six post-doctoral researchers who have moved on to academic posts as assistant professors, so the knowledge base about this research is expanding."