Technological advances in psychiatric disease treatment and prevention

Professor Mill specialises in characterising genomic variation in the human brain, using cutting-edge methods. His team generates maps in the brain detailing the differential expression of genes across the different cell types in the central nervous system and using these annotations to ask questions about the mechanisms involved in disorders such as schizophrenia, Alzheimer’s disease and motor neurone disease. Professor Mill said: “The brain is comprised of a mass of different type of cells. Until now, it has been very hard to identify which of these is implicated in specific diseases. We’re using novel methods to “purify” these different cell populations, characterising which genes are activated at different points in development and identifying which genes are not functioning properly in disease. These studies are identifying a huge number of novel genes that might be important in the disease process, elucidating new mechanisms and identifying potential drug targets.”

The team is also using these genomic maps of specific brain cell-types to develop a test to identify early signs of neurodegeneration. Collaborating with the Exeter Sequencing Facility, the team’s novel assay can detect genetic material originating from the brain in circulating blood, providing an early indicator of disease. For any future treatments to be effective, we will need to intervene as early as possible.

At the University of Exeter’s Mireille Gillings Neuroimaging Centre, early disease identification is one of a range of research areas for Dr Heather Wilson, Senior Research Fellow and Lead of Imaging Methodology. The facility incorporates cutting-edge PET/CT and MRI scanners to support multidisciplinary clinical research and clinical trials. Importantly, these scanners are specifically dedicated to clinical research. “We have among the best scanning technology in the country, allowing us to conduct world-leading molecular imaging research in brain disorders to help drive forward breakthroughs in understanding disease aetiology, pathophysiology, how patients respond to treatments and biomarker discovery,” Dr Wilson said.

The technology means the University’s Neurodegeneration Imaging Group can understand some of the earliest disease related changes in living patients with neurodegenerative disorders including Huntington’s, Parkinson’s and Motor Neuron Disease. The group’s large portfolio of research studies is at the forefront of innovations in the identification of novel targets for pharmacotherapy, biomarker discovery and understanding disease mechanisms. The ability to reliably identify patients early in the disease, even in preclinical stages, and track their progression, using in vivo markers, could help to provide temporal and spatial maps of disease pathology. Molecular neuroimaging provides a unique opportunity to identify patients early when therapeutic intervention might be most effective, and to improve the stratification of patients into targeted clinical trials based on underlying molecular pathology, as well as providing outcome measures with greater sensitivity.

The team can identify new drug targets and examine the effects of a particular drug to see how it behaves at a molecular level, helping to accelerate drug development. Dr Wilson said: “We’re investigating new biomarkers, and new targets for disease modifying therapies in diseases including Parkinson’s and Motor Neurone Disease, and we’re running clinical trials testing the effects of different drugs. This technology can be applied to a range of other brain disorders, including schizophrenia.

“Our state-of-the-art Neuroimaging Centre enables interdisciplinary collaborations with academic and industry partners to bridge the gap between basic and clinical research driving faster translation into drug development and clinical applications for patients.”

This interdisciplinary approach as at the heart of the University of Exeter’s Living System’s Institute. Dr Akshay Bhinge, Senior Lecturer in Clinical and Biomedical Science, specialises in stem cell research, which seeks to find new treatments that will work in humans more effectively than animal research has so far produced. “Animal and human cells are similar, but they’re not the same,” said Dr Bhinge. “Our method uses human induced pluripotent stem cells – that’s an incredibly powerful tool which means we can take skin or blood cells from a patient and turn these cells into a stem cell, then create any kind of cell we want, including different brain cells. We’re working with human brain cells, and we can look in minute details at how those cells behave, and how that contrasts whether they’re affected by disease.” 

In motor neurone disease, the techniques have revealed that neurones look and connect differently than those generated from people without the disease. “These are live neurons, so we can follow their life process in a dish,” said Dr Bhinge. “We can see how they behave when exposed to different drugs or genetic perturbations, which is a promising route to finding new treatments for disease.”

The lab utilises genomics and microscopic techniques, and results are cross referenced with patient data. “We have a critical mass of outstanding researchers across different disciplines working on complex neurologicaldisorders, which generates very exciting outcomes and opportunities,” Dr Bhinge said.