Philips Research Technology Backgrounder

Organon and Philips team up to study drug effects at the molecular level

Royal Philips Electronics, one of the world’s leading players in medical imaging, is collaborating with N.V. Organon (Oss, The Netherlands), a leading biopharmaceutical company, in the development and application of non-invasive imaging techniques as biomarkers of disease and as a means of studying new drugs and therapies for the treatment of psychiatric disorders such as depression and schizophrenia.

Clinical depression currently affects around 6% of people in the western world, and while the incidence of schizophrenia is lower (approximately 1%), these two conditions, together with the full range of other psychiatric disorders, cause enormous suffering to patients and caregivers and result in a significant economic burden to society. In addition to improving the quality of life for patients, the development of effective drugs to treat such disorders will therefore have a highly beneficial impact on caregivers, the economy and society as a whole.

Although the exact causes and mechanisms underlying psychiatric disorders remain unknown, it is thought that such disorders arise through an imbalance of chemical messengers (so-called neurotransmitters) in the brain. Drugs for the treatment of psychiatric disorders correct the neurotransmitter imbalance and subsequent processes in the brain. In order to diagnose psychiatric disorders, clinicians have to rely on qualitative clinical rating scales of emotion. Such scales are inherently unreliable and alternative biomarkers (specific molecules or readouts that can be measured as an indicator of biological function) for psychiatric disorders are currently problematic or lacking.

Due to a highly selective and effective barrier between the brain and the bloodstream, very few biomarkers for brain dysfunction can be determined by analyzing blood samples. Although some biomarkers can be detected by analyzing cerebrospinal fluid extracted via a lumbar puncture (spinal tap), the costs and risks associated with such an invasive procedure are significant. As a result, pharmaceutical companies undertaking clinical trials to develop new drugs for psychiatric disorders typically have to rely on the same qualitative clinical rating scales. Because these scales are inherently variable and because individual patients can respond to the same drug in very different ways, with improvements in psychiatric disorders often taking weeks or months to become apparent, new ways to diagnose and monitor the effectiveness of drugs for the treatment of psychiatric disorders are required.

Personalizing patient therapy
The molecular imaging techniques being developed by Philips Research and Organon will allow direct measurement of changes in neurotransmitters within the brain as a result of drug treatment and provide quantitative readouts, or biomarkers, of brain function. The success of this research collaboration will rely on Organon’s expertise in neurological drug discovery and the use of its proprietary compound libraries to identify specific biomarkers plus Philips Research’s ability to apply new diagnostic imaging techniques to identify and quantify these biomarkers at the molecular level. It is expected that all stages of the drug discovery and development process, together with clinical management of patient care, will benefit from their research results.

The advanced imaging technology developed by Philips Research will permit the non-invasive measurement of brain activity or ‘fingerprints’ of existing drugs to be generated. By providing a better understanding of how these drugs work, this information will enable Organon to develop novel drugs with improved efficacy and reduced side-effect profiles. Just as importantly, it will improve the decision making process as compounds progress through the clinical phase.

Together, it is expected that such advances in non-invasive imaging will increase the success rate associated with the identification of new drugs and ultimately lead to smaller, more focused, clinical trials. These smaller, more focused clinical trials will help Organon to select the best compounds for further study and speed up the clinical phase of drug development, ultimately leading to faster approval and registration. Following approval, such imaging-based technologies will enable clinicians to prescribe therapies personalized to individual patients through the new paradigm of companion diagnostics. Developed by Philips, such companion diagnostics can be used to pre-screen patients for their response to specific drug treatments, and to measure the effect of therapeutic intervention in order to confirm drug effectiveness and optimize dose regimes.

Creating the image
The imaging modalities that Philips Research will use to enable these new drug discovery techniques and companion diagnostics include Magnetic Resonance Imaging (MRI), Positron Emission Tomography (PET), Single Photon Emission Computed Tomography (SPECT) and Optical Imaging. Functional Magnetic Resonance Imaging (fMRI) will be used to create a reference database of existing drugs and to classify novel compounds, while Magnetic Resonance Spectroscopy (MRS) studies will help to assess the effect of drugs on neurotransmitter concentrations in the brain. PET and SPECT experiments will aim to image the effects of new drugs on specific biochemical and neurotransmitter processes at the molecular level through the development of novel PET/SPECT tracers.