Lead by Innovative Medicines Initiative, the Project Aims to Identify Biomarkers for Mental Disorders
Success of first part of project has led to funding from the Innovative Medicines Initiative 2 Joint Undertaking for a new project that will build on PRISM’s successes
Focus on Alzheimer’s disease, schizophrenia and major depressive disorder
14 companies and institutes will cooperate on project
Brain research and advocacy non-profit Cohen Veterans Bioscience (CVB) announced today that it joined the PRISM 2 consortium as as a designated associated partner of the Innovative Medicines Initiative (IMI).
The new PRISM 2 project, “Psychiatric Ratings using Intermediate Stratified Markers 2,” aims to identify quantitative biological features common across Alzheimer’s disease, schizophrenia and major depressive disorder, opening the possibility of developing targeted treatments irrespective of traditional diagnosis.
Building on the success of innovative research by the original PRISM project, the Innovative Medicines Initiative 2, a joint undertaking between the EU and the European Federation of Pharmaceutical Industries and Associations (EFPIA), has backed the program with funding for a new project to explore the underlying biology across the diseases.
Most mental health or neurological problems are only diagnosed when the patient begins to show symptoms‚Äì for example when they begin to sink into depression, or when Alzheimer’s disease starts to affect their memory. The ability to understand the biological causes of mental health conditions before clinical onset ‚Äì which may lead both to early diagnosis and targeted treatment – has long been a “holy grail” of neuroscience.
Magali Haas, MD, PhD, President and CEO of Cohen Veterans Bioscience, said:
“We are delighted to partner in this critical initiative. To advance precision solutions for patients we need transdiagnostic approaches and objective biomarker assessment tools as the PRISM 2 initiative develops them. Often individuals with different diagnoses share common symptoms. The emphasis on quantitative, as opposed to qualitative, categorical disease parameters, offers significant benefits for the advancement of new therapeutic solutions for these conditions.”
These disorders are also much more complex than often recognized. Indeed, there are many symptom domains that do not align neatly with traditional diagnoses but appear in individuals with a variety of different diagnoses. As people with Alzheimer’s do not only exhibit impairments in memory, people with schizophrenia do not only experience psychosis.
The original PRISM project has taken the first steps at developing a suite of biological tests, including Magnetic Resonance Imaging (MRI), blood tests, smartphone monitoring and Electroencephalogram (EEG), which will allow more objective diagnosis of the conditions, and indicate which brain mechanisms are involved, potentially identifying targets for tailored treatment.
PRISM launched in 2016, worked with patients to measure brain and behavioral activities using a variety of new and existing techniques. The project focused on Alzheimer’s disease and schizophrenia and used social dysfunction, which is common to both conditions, as a key to access the underlying causes. This part of the project has successfully identified measurable biological indicators related to traditional diagnoses of schizophrenia and Alzheimer disease. However, the unbiased approach in PRISM also allowed a novel “transdiagnostic” link between a neural circuit and social dysfunction to be identified. The new PRISM 2 project aims to probe these findings more deeply as well as casting the net more broadly to include Major Depressive Disorder.
Social dysfunction is one of the earliest indicators of the onset of several common psychiatric and neurological disorders but it is a symptom that may be caused by very different neurobiological processes. People with social dysfunction tend to retreat from friends and family, as well as from social networks at their workplaces. The underlying causes and mechanisms remain unknown.
By probing large genetic databases, such as the UK BioBank, the team found 19 genetic variations linked strongly to social dysfunction. Intriguingly, all of these 19 genetic variations were confirmed as being linked to protein expression in the specific circuit identified in the study.
These findings led to the IMI agreeing to a ‚Ç¨7.9m funding allocation to build on the results in a new project.
Academic project coordinator and Professor of Behavioural Neuroscience at the University of Groningen, Prof. Dr. Martien Kas, said:
“PRISM has been able to apply new statistical and monitoring tools to unpick biological associations with mental health and neurological conditions. For example, using GPS and call logs on smartphones show how much people move and interact, which indicates social functioning status. We can relate behavioural traits to findings from MRI and EEG: in fact we have identified over 4000 relevant biological markers. We are now beginning to identify patterns which associate these markers and behavioural traits with conditions such as Alzheimer’s disease and schizophrenia, and this is what has led the IMI Joint Undertaking to support phase 2 of the project.
PRISM 2 will aim to determine just how reproducible and accurate our initial findings are, especially in schizophrenia and Alzheimer’s disease, and we will investigate generalizability of the findings to a third indication, namely Major Depressive Disorder. The ultimate aim is to translate our findings into practical diagnosis and treatment.”
14 institutes and companies in the EU, the UK, and the USA will cooperate on PRISM 2.
IMI Executive Director, Dr Pierre Meulien, said:
“By bringing together partners including patients, universities and companies, PRISM succeeded in shedding new light on some of the underlying causes of schizophrenia and Alzheimer’s disease. PRISM 2 will build on this work and if successful, could significantly change how we see and treat mental illness.”
Industrial project leader and Head of Department CNS Diseases Research at Boehringer Ingelheim, Dr. Hugh Marston, said:
“We do need to focus, in an unbiased manner, on the problems that neuropsychiatric patients actually suffer from. PRISM was an excellent example of patients, academics, CROs and major pharma coming together to try to shed new light on these life changing disorders. I am excited that the findings of PRISM’s paradigm changing approach to mental health have led to the extension of this project. We hope that our research will yield better diagnosis and treatment choices that transform the lives of people with Alzheimer’s disease, schizophrenia and Major Depressive Disorder.”
List of participating companies and Institutes, PRISM 2