The promise and challenges of biomarkers for mental illnesses
Our CEO, Professor Ian Cooke was recently published in The Conversation on “The promise and challenges of biomarkers for mental illnesses” http://theconversation.edu.au/the-promise-and-challenges-of-biomarkers-for-mental-illnesses-10195
The article was based on a longer speech given by Professor Cook at the Cooperative Research Centre breakfast with the Health Minister Tanya Plibersek at Parliament House Canberra in August 2012.
TRANSCRIPT OF SPEECH GIVEN AUGUST 2012
Minister, Honorable Members and Senators, ladies and gentlemen.
Thank you very much for this opportunity to speak about the CRC for Mental Health.
We were established last year to progress the early detection and effective treatment of the most tragic forms of mental illness, including Alzheimer’s Disease, Parkinson’s Disease, schizophrenia, bipolar disorder and major depressive disorder. Our participants include Australia’s leading academic and clinical neuroscientists, plus major public and private sector providers of aged care and mental health care services. We have the world’s largest pharmaceutical company Pfizer, which has long been a strong supporter of basic and applied medical research in Australia, plus several of the world’s smallest – based in Melbourne and Perth.
Our objective is simple – to put it bluntly, we want to be able to stop people from losing their minds.
Our principal focus is on the discovery and development of biomarkers to help diagnose mental illness before the onset of irrecoverable mental decline and assist in the development and deployment of new drugs, patient management strategies and, ultimately, new population heath initiatives.
As a community we are used to the concept of chronic, as yet incurable disease. We know people of all ages who cope with cancer, some being lucky enough to survive, others who die after what we usually refer to as a courageous battle. We venerate the affected individuals, their carers and those who seek cures. We are disappointed in our inability to prevent these forms of suffering, but we can track incredible and recent progress in prevention and treatment and we are confident that science will continue to make things better.
We see, as a benchmark, the outstanding successes of cardiovascular medicine over the past decades. We now understand the causes; have in place effective drugs and lifestyle modification strategies and are able to implement powerful preventive programs at the level of the population. Critically, we have simple biomarkers, such as blood pressure and blood cholesterol, which enable us to measure risk and response to intervention, both in individuals and at the level of the population.
By contrast, as a community we struggle with the concept of mental illness. We are naturally uncomfortable with people whose reality is different from ours, especially when that was not always the case. We want to hear the great stories of resilience, of recovery, but they are few and definitely atypical.
Instead, the overwhelming reality, the one that our CRC seeks to address, is of individuals who are losing their minds – who slip away from their lifetime experience, their personality, their creativity, their dreams, their relationships, their ability to love and feel loved. This reality is about individuals whose gradual mental deterioration often creates an enormous emotional and economic burden for the people who love them the most, with the consequence that the responsibility for day-to-day care must pass to others who, while dedicated, typically know little about past lives and personalities of the many individuals for whom they must care and often do not know much about the nature of the disease that affects them.
At present, we have little to offer. Our methods of diagnosis are complex and to a degree subjective. Our therapeutic armamentarium is sparse – the few drugs that are available to treat patients with mental illnesses are typically old and only partially effective. We have no effective strategies to prevent mental illness. We have no biomarkers to guide us.
This is a great year to be a physicist in Australia. We have Brian Schmidt’s Nobel Prize, we have the announcement of verification of the existence of the Higgs boson and we have the recent decision on the location of the Square Kilometre Array. We have a public that is entranced by esoteric concepts such as dark matter and dark energy and eager to learn more.
Astrophysics and particle physics are probably the stand-out examples of the successes of big cooperative science – in which teams of extraordinarily capable individuals are able to subjugate individualism and ego to design and implement large-scale long-term research programs to pursue the really big challenges – to find the tiny, meaningful signal among the noise
In my hand here I hold a human brain. It is the location of personality, emotion, learning and wisdom in a unique individual.
This brain contains 100 billion nerve cells – approximately the same as the number as there are galaxies in the observable universe. Each cell makes on average, 1000 connections with other neurons, representing the potential for 100 trillion simultaneous information transactions.
Mental illness is the result of aberrant biological function in this dynamic structure – some biochemical process gone astray.
This is an image of a section of a human brain taken from an individual who suffered from Alzheimer’s disease, by far the most common cause of dementia in the community.
We do not know what actually causes Alzheimer’s disease. Age is the greatest single risk factor. Other significant risk factors include family history (genetics), gender (female) and various life exposure factors including head trauma, cardiovascular disease and living alone.
In this image you can see the neuroscientist’s version of dark matter. This is the dominant distinguishing feature of the brains of Alzheimer’s patients– the deposition in the brain of plaques of amyloid protein. Here we see small levels of amyloid in the brain of a cognitively normal aged person and here is the brain of a person with Alzheimer’s Disease.
It looks menacing. Yet the actual amount of this abnormal material in an Alzheimer’s brain is very small – about 10 milligrams. It may take 20 years for this amount of amyloid to accumulate in the brain of an Alzheimer’s patient. While this may be our strongest lead, we have yet to convincingly explain dementia in terms of amyloid protein dysfunction in the brain and new drugs designed to reduce amyloid load have not yet proven effective in slowing the progression of dementia in Alzheimer’s patients.
We face similar frustrations in understanding and trying to deal with other forms of mental illness – we cannot tie the illness to a specific biological process gone wrong and thus we are not in a position to treat the illness effectively by rectifying the aberrant biology.
Every biological process creates a biological signal – the molecular product or products of a biochemical reaction.
An aberrant biological process must create a signal that is different in some way from normal processes. These signals are inherently detectable in one of more of the body’s biological fluids – the CRC’s aim is to discover them among the noise of the myriad signals arising from normal biological processes and determine their relationships to disease processes in different forms of mental illness.
A fundamental challenge is to look in the right direction. To discover useful biomarkers, we must study not only individuals who have a defined mental illness but, most critically, individuals who will one day develop mental illness, but well before their symptoms become apparent.
The CRC for Mental Health has been created on the foundation of what is generally regarded to be the most successful, prospective study of ageing and dementia in the world – AIBL – the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing. It was established 6 years ago, as a joint venture by our 5 major public sector research participants.
AIBL has over 1000 participants aged over 60 and includes healthy controls, individuals with mild cognitive impairment and individuals with diagnosed Alzheimer’s Disease. They are assessed every 18 months – including comprehensive physical, clinical psychological and lifestyle assessments, brain imaging and samples taken for investigation of potential biomarkers. The 54-month assessments are in progress and will be completed next year.
The CRC for Mental Health was funded to analyse the AIBL samples for potential biomarkers that will enable us to predict the occurrence of Alzheimer’s Disease and inform about progression of the disease.
In addition, we have established new prospective cohorts, based on the AIBL model and protocols, to enable us to investigate potential biomarkers of Parkinson’s Disease and treatment-resistant schizophrenia. Furthermore, we are leveraging other major Australian prospective cohort studies – including the WA Family Study of Schizophrenia (10 years) and the famous Geelong Osteoporosis Study (>15 years) to extend these biomarker investigations.
What distinguishes our approach in AIBL from other prospective studies elsewhere is its extraordinary rigour in subject management and sample collection – to reduce noise, so that we can detect faint, but real signals – the equivalent of astronomers placing their most sensitive telescopes on vibration-proof settings far away from any human sources of radiation (light). This rigour is why we have Pfizer by our side. We are applying this world leading approach to our new prospective cohorts for other forms of mental illness.
Finally – here is an example of what we are searching for – a potential biomarker for Alzheimer’s disease that can be detected in the blood.
This is a scan of proteins in blood taken from Alzheimer’s patients and healthy controls. It shows only the very low abundance proteins – all of most abundant species have been filtered out. Proteins that occur in both healthy and Alzheimer’s individuals are coloured yellow, those found only in healthy individuals are green and those only in AD individuals are red.
Here we have a potential marker – a tiny red spot – a single species of protein that appears only in Alzheimer’s individuals but which is absent from individuals who remain cognitively healthy.
We have a long way to go before we can prove the value of this particular discovery or any other discoveries of this form that we might make. It might ultimately lead us to a biochemical pathway that we can modify with a new drug, or perhaps with something as simple as a dietary supplement or lifestyle modification. However, the CRC for Mental Healthis now positioned to pursue these opportunities and translate them new products and new approaches to clinical management and disease prevention that will benefit potentially millions of individuals and generate ongoing social and economic benefits for Australia.
Thank you for your attention.