Since January 2015, Tübingen has been home to a Centre for Personalised Medicine (ZPM). Twenty-three institutes and hospitals have joined forces to improve diagnosis of disease and develop individualised treatments for patients with a variety of diseases. In parallel, the centre also develops new diagnostic strategies. This means, for example, that data derived from the analysis of the entire genetic material of cells, proteins and metabolic processes are taken into account when stratifying patient therapy.
"It is not that easy to sum up what personalised medicine actually is," says Prof. Dr. Nisar Malek, director of the ZPM, going on to add that the Centre has in fact three main goals.
"On the one hand, we hope to be able to increase our understanding of diseases with the diagnostic possibilities offered by state-of-the-art 'omics' technologies. On the other hand, we also want to use functional imaging methods to improve diagnoses on an individual patient level. This includes more accurate companion diagnostics tests that enable us to react much earlier than before to changes in disease progression. Finally, we want to combine the results from omics analyses, imaging and clinical findings in order to determine the optimal treatment approach for patient groups or individual patients," explains Malek.
The interdisciplinary experience of the 23 departments and institutes of the University of Tübingen's Medical Faculty that come together in the ZPM is key to making this project work. Malek sees the comprehensive approach, which involves virtually all medical disciplines, the natural sciences and information technologies, as one of the ZPM's key selling points. Currently, Germany only has a handful personalised medicine centres, with most of the centres only focusing on one specific topic. We hope that our approach will take us to the forefront of research into the causes of disease in individuals and the development and testing of individualised treatments," he concludes.
In order to effectively and optimally integrate omics data, i.e. data derived from the analysis of the entire genetic material of cells (genomics), proteins (proteomics) and all metabolic processes (metabolomics) into diagnosis and therapy, the centre has secured the support of the Centre for Quantitative Biology (QBIC).
The Centre for Quantitative Biology (QBIC) at the University of Tübingen is headed up by Prof. Dr. Oliver Kohlbacher. The centre pools data produced in the University of Tübingen's hospitals and research institutes with state-of-the-art, high-throughput technologies. The QBIC team analyses and prepares the data for the ZPM. Imaging data are provided by the Department of Preclinical Imaging and Radiopharmacy led by Prof. Dr. Bernd Pichler. Pichler's team is developing pioneering technologies such as a device that combines PET (positron emission tomography) and MRI (magnetic resonance imaging) and provides highly accurate images and information from inside the body.
"To be able to quickly and simply link imaging data with omics data, we are establishing a new database in which anonymised patient data are stored ontologically. In June 2015, our hospitals will activate the first accounts. We are currently providing the patients with the information that is necessary to make an informed consent," says Malek.
His vision: such models will in future provide the basis for the optimal treatment of patients predisposed to a particular disease. In the case of heart failure, this concept will be able to identify drugs that have the greatest chance of success in a particular patient, either on their own or in combination with other drugs.
However, this concept does not fit into the current medical treatment approval and reimbursement system. Malek explains this using cancer treatment as an example. "Suppose we have a patient with cholangiocarcinoma, and we then simulate therapy using all 30,000 drugs approved for human treatment. If the simulation suggests that the patient would best respond to substance XY, this particular drug may well be approved for a number of tumours, but unfortunately not or not yet for the treatment of cholangiocarcinoma."
A few demonstrator projects are already underway, ranging from heart failure and eye diseases to different types of cancers. The projects were originally initiated by the Clinical Research platform established by the University's institutional strategy under the German government's Excellence Initiative. They now come under the ZPM.
Malek uses heart failure to explain how the Centre works. "We have established so-called Molecular Boards in order to gain an understanding of heart muscle diseases on all levels. We are, for example, looking at the genetic constellation of patients in order to find out why they became ill. High-throughput screening and sequencing is thus used in genetic and molecular analyses of patient DNA. In addition, we also use omics data and information derived from PET/CT and PET/MRI images. Using mathematical models across several orders of magnitude helps us correlate the different parameters with each other," says Malek.
Malek is convinced that in the not-too-distant future doctors will experience a paradigm change in the diagnosis and therapy of diseases. He also believes that the procedure for obtaining marketing authorisation for drugs will have to be completely revamped. "The current principles of obtaining drug approval will no longer work in cases where it is impossible to recruit the necessary number of patients with a specific gene signature. Pesonalised medicine will change the diagnosis and treatment of disease forever, and this will affect all areas. Health insurance companies will also have to deal with new challenges and we are trying to sensitise them for the upcoming changes. It goes without saying that patients' associations will then also require healthcare providers to change their way of dealing with reimbursement and other issues."
However, Malek does not believe that the cost system itself is at risk. "The common belief that personalised medicine will lead to dramatically rising costs is definitely not right. Just think about the horrendous cost of medicines and treatments that have little or no effect; therapies tailored to the requirements of individual patients would avoid such costs." Malek also stresses that personalised medicine, along with its full arsenal of analytical methods, will not be used for all diseases. There is no reason to use personalised medicine in the case of monocausal diseases. It would be too expensive. Simple bacterial diseases can easily be treated with antibiotics; the application of individualised analyses would disproportionate to the benefits. Precise understanding of the cause of a bacterial infection is not necessary in order to treat it successfully.
However, when it comes to complex diseases, the situation is different. In fact, complex analyses are very important when it comes to conditions with various causes. Malek explains why, again using cancer as an example. "A cancer such as pancreatic cancer involves a large number of different cells, and we basically need to treat many diseases simultaneously on the molecular level. Therefore, knowledge and experience from widely differing research fields need to be integrated in order to develop new, individual treatments. The one size fits all rule where, for example, broad-spectrum antibiotics are used, cannot be applied to cancers and other diseases that have several causes. However, in order to treat three or four problems simultaneously, individualised medicine is definitely the way to go."
Centre for Personalised Medicine - ZPM
The University of Tübingen's ZPM consists of five research areas:
I High-Throughput MethodsSpeaker: Prof. Dr. Olaf Rieß, Institute of Medical Genetics and Applied GenomicsII Complex DiagnosticsSpeaker: Prof. Dr. Oliver Kohlbacher, Centre for Bioinformatics, Centre for Quantiative Biology and Department of Computer ScienceIII Functional and Molecular ImagingSpeaker: Prof. Dr. Bernd Pichler, Institute for Preclinical Imaging and RadiopharmacyIV Therapy DesignSpeaker: Prof. Dr. Lars Zender, Department of Internal Medicine 1 and Section for Gastrointestinal OncologyV Experimental TherapySpeaker: Prof. Dr. Nisar P. Malek, Department of Internal Medicine 1