Team:KU Leuven/HP/Gold Integrated

Human practices: Integrated and Gold

In HEKcite we create an oscillating HEK-cell, but for what purpose? Therapeutic drug monitoring is our answer. In the treatment of multiple severe diseases, a stable concentration of drugs is crucial. Steady blood levels determine therapeutic outcomes and increase survival rates. Currently, the most common therapeutic drug monitoring technique is blood sampling. For patients who need lifelong observation, the numerous hospital visits and frequent blood samplings can have a negative effect on the quality of life. Therefore, we develop a system that allows patients to determine the level of drugs at home. Furthermore, the ease of these measurements allows for daily or even continuous analysis.

Using this dynamic data collection instead of the static measurements performed in hospitals today, we might increase both therapeutic outcomes and quality of life of patients. In order to investigate the different views on our projects we talked to specialists in several fields where therapeutic drug monitoring is of great importance: transplantations, psychotics and epileptics. Three specialists have provided insights in how they expect our project will influence the lives of their patients and future treatments. We used this information to further shape our project.

Professor Diethard Monbaliu MD, PhD

Professor Monbaliu is a reputable abdominal transplant surgeon, at the department of microbiology and immunology at UZ Leuven. He is also responsible for a course on topographical and radiological anatomy and supervises several thesis students.

Professor Monbaliu confirmed our suspicion that there is a need for a more dynamic measurement. In addition, he suspects that it could lead to a better evaluation of patients’ compliance. Together, these advances could result in fewer transplant rejections. He has also brought our attention to a novel and more prevalent immunosuppressant drug, tacrolimus. Finally, he mentioned that patient variability is an issue in his field, and that our device should take this into account. Want to learn more? Press for more details.

Professor Chris Bervoets MD, PhD

Professor Chris Bervoets is a psychiatrist. He is responsible for the department of transcranial magnetic stimulation, the department of deep brain stimulation and the department of compulsive disorders within the UPC (University Psychiatric Center) of KU Leuven. Additionally, he conducts research on neuromodulatory treatments for various psychiatric disorders.

While investigating different branches in medicine that could benefit from improved therapeutic drug monitoring, our attention was drawn to psychiatry. In this field, there are several drugs, for example lithium, that affect ion channels and could therefore be measured directly by our system. These aspects spiked our interest, and to learn more we contacted the specialist professor Chris Bervoets, who gave us some valuable insights in the difficult world of psychiatry.

Professor Wim Van Paesschen MD, PhD

Professor Wim Van Paesschen is a neurologist specialized in epilepsy. He also is head of the epilepsy research laboratory of the UZ Leuven, and is a lecturer at the faculty of medicine.

Professor Van Paesschen confirmed that therapeutic drug monitoring is important for anti-epileptic compounds and mentioned the necessity of verifying patient compliance. He was very enthusiastic about the project, and even suggested other possible applications for the HEKcite cells.

Professor Peter Sinnaeve MD, PhD

Prof. Dr. Peter Sinnaeve is a cardiologist who is specialized in acute cardiology, intensive care cardiology, interventional cardiology and pericardium disorders. Next to this, he is a part-time teacher at the Faculty of Medicine of KU Leuven.

After our meeting with professor Sinnaeve we learned that therapeutic drug monitoring of ivabradine is not clinically relevant within the field of cardiology. However professor Sinnaeve reassured us that using ivabradine as a proof-of-concept is still valuable. Next to this, he mentioned the crucial value our project could have in measuring drug concentrations during phase 1 clinical trials where a strict follow-up and good patient compliance is of great importance.

Professor Filip Bouckaert

Filip Bouckaert is a geriatric psychiatrist and member of the University Psychiatric Center (UPC) at KU Leuven. He is specialised in geriatric psychiatry, anxiety, mood disorders, psychosis and electroconvulsive therapy (ECT).

As psychiatry seemed a very interesting target for therapeutic drug monitoring, we contacted Filip Bouckaert for a second opinion. He suspects that only a small amount of psychiatric patients, people severely affected by bipolar disorder, would benefit from our project. However, he expects that their quality of life would be hugely improved.

Specialists Professor Chris Bervoets Professor Peter Sinnaeve Professor Diethard Monbaliu Professor Wim Van Paesschen Course of action before the meeting TDM of lithium for patients with bipolar disorder. TDM of ivabradine for patients with sever heart failure. TDM of anti-epileptics such as ethosuximide for patients with daily and/or severe seizures. TDM of cyclosporine used as a immunosuppres-sant after organ transplantation. Information gathered during the meeting TDM is of importance and our project has a potential application in measurement of receptor occupancy. TDM of ivabradine is not useful in treatment but can be used as a proof-of-concept. However, TDM is important during phase 1 clinical studies. TDM of ethosuximide would be of importance in the treatment of epilepsy and HEKcite could be of use in personal medicine and research. TDM of immunosuppressants is needed.However tacrolimus is now the most frequently used immunosuppressant instead of cyclosporine. Additionally, our system could help verify patient compliance. Integration of the meetings During the course of our project, we decided to proceed with the calcium, potassium and HCN channel to establish a rhythm in the HEK cells. This means that using lithium-carbonate, an inhibitor of sodium channels, to change this rhythm was no longer possible. However, for future research sodium channels could also be implemented to establish an intrinsic rhythm which means that also the lithium-carbonate concentration could be measured by HEKcite. After this decision, we first started doing experiments with ivabradine, an antagonist of the HCN channel, since this seemed the most logical step forward to change the established rhythm. However, after recieving the input of professor Sinnaeve stating that TDM of ivabradine is not necessary in treatment, we decided to do parallel experiments with different drugs. We did not discard ivabradine completely since professor Sinnaeve stated it’s importance as a proof-of concept. Regarding the input we received from both professor Van Paesschen and professor Monbaliu, we started to use cyclosporine and ethosuximide to ensure the societal relevance of our project. Our decision to use cyclosporine instead of tacrolimus was purely financially motivated, tacrolimus appeared to be too expensive to use in our research.