Issue 87, June 2017
bullet Personalized Medicine
bullet Personalized Antibiotherapy
bullet The Smart Drug that Clears Fat from Liver and Blood
bullet The Cellular System that Makes the Battle Against Rare Diseases Personal
Personalized Medicine
Most medical treatments are designed for the average patient and result in a one-size-fits-all approach.
Today, with substantial amounts of data available, researchers can analyze information about our genes, our family histories, and many other health conditions to gain a better understanding of the types of treatment that work best for specific segments of the population. Having the capability to look at a patient on an individual basis allows for a more accurate diagnosis and a more individualized treatment plan.

Personalized medicine, or precision medicine, holds enormous promise, while it also requires knowledge, trust, and collaboration between geneticists, biologists, computer scientists, startups, and patients. Personalized medicine's aim is not to optimize the health of one patient, but to improve outcomes on a population-wide scale. For this reason, social, cultural, environmental, and privacy factors need to be taken into account.

The German Minister of Education and Research, Johanna Wanka believes that, "With the help of digitization, personalized medicine can become a reality." The challenge is how personal health-related data will be handled. This includes how the data will be shared between different institutions, such as hospitals, health insurers, and employers. The technology is available and several targeted therapies are already underway. If our institutions and regulatory frameworks are strong, then the potential benefits will likely outweigh the ethical risks.

This month's newsletter highlights new developments in the German personalized medicine landscape. For example, the Technical University of Munich (TUM), the Helmholtz Association, and Indiana University have developed a smart drug that safely clears the liver of fat and prevents blood vessels from clogging up. Our interview partner this month, Prof. Dr. med. Nisar Peter Malek, foresees a combination of different technologies that will be used to provide information on the status of individual patients, as well as the introduction of artificial intelligence applications in personalized medicine.

In recent years, the number of life-threatening infections that are difficult to treat with antibiotics has drastically increased due to the prevalence of multidrug-resistant bacteria. One of the main reasons for this is the all-too-frequent and inappropriate use of antibiotics in human medicine. For example, a therapy may be critically affected by low antibiotic doses, which consequently promote the emergence of multidrug-resistant bacteria. However, overdosing would raise the risk of toxic side effects without additional anti-infective benefits. In this context, a personalized antibiotherapy, including the drug dose and dosing intervals for each individual, is a promising approach for antibiotic treatment by improving its efficiency.

Researchers from the University of Freiburg Laboratory for Sensors at the Department of Microsystems Engineering (IMTEK) and Laboratory of Synthetic Biology at the Centre for Biological Signalling Studies (BIOSS) have developed a biosensor platform that can quantify up to eight different antibiotics in human blood or other fluids simultaneously. Its major advantages are the facile and low-cost fabrication and the simple applicability as a "plug-and-play system" for a broad range of different substances like biomarkers or drugs. The sensor platform could eventually be used for medical diagnostics, especially for multiplexed point-of-care testing (xPOCT) in a doctor's office, or at a home, as well as for environmental and food monitoring. In a recent study, its applicability for xPOCT was demonstrated by measuring two antibiotics, tetracycline and streptogramin in patients' blood within only 10 minutes, from sample to result. In this study, the system is combined with naturally-occurring sensor proteins in multidrug-resistant bacteria to recognize various antibiotics and activate their defense mechanisms. These bacterial sensors react quickly, sensitively, and specifically against antibiotics and thus are ideal for analytical testing. The researchers believe that this technology could soon pave the way for personalized antibiotherapy.

Source & Image: University of Freiburg

Scientists from the Helmholtz Zentrum München, the Technical University of Munich (TUM), and Indiana University have developed a 'smart' drug that safely clears the liver of fat and prevents blood vessels from clogging up. Similar to a Trojan horse, the drug enters the liver with a trick; it uses a pancreatic hormone as a vehicle to transport a thyroid hormone to the liver, while keeping it away from other organs. Once delivered, the drug improves the cholesterol and lipid metabolism, while avoiding typical side effects of the thyroid hormones.

The constant rise in obesity and diabetes represents a major burden to modern societies. Fatty liver and atherosclerosis are frequent consequences of these metabolic diseases. The development of an efficient and safe medicine that could reverse obesity, insulin resistance, fatty liver, and atherosclerosis remains a major scientific challenge and is a global priority.

The international research team is led by metabolism experts Professor Matthias Tschöp, Chair of Metabolic Diseases at TUM and Director of the Institute for Diabetes at the Helmholtz Zentrum München, Timo Müller from the Helmholtz Zentrum München, and Richard diMarchi from Indiana University. Their team recently reported in the prestigious journal Cell that the liver-specific delivery of the thyroid hormone T3 by using glucagon corrects obesity, glucose intolerance, fatty liver disease, and atherosclerosis without causing adverse effects in other tissues. "While the ability of T3 to lower cholesterol has been known for centuries, deleterious effects, in particular on the skeleton and the cardiovascular system, have until now limited its medicinal utility," says Brian Finan, the first author of the manuscript.

Source & Image: Helmholtz Zentrum München  


Some diseases are currently untreatable because we lack animal models to fully understand symptoms or to test possible drugs. One example is mitochondrial disease, which is a rare condition caused by defects in the "cellular powerhouse." Alessandro Prigione of the Max Delbrück Center for Molecular Medicine (MDC) has recently developed a cell-based and truly personalized drug screening strategy .
Mitochondria produce most of the cell's energy and are unique, since they carry their own DNA. When they fail due to mutations in mitochondrial genes, cell injury and even cell death may follow. Parts of the body, such as the heart, brain, muscles, and lungs that require the greatest amounts of energy are among the most vulnerable.
Therefore, Prigione studies the cell types that are most affected by these diseases, such as neural cells. His strategy involves extracting skin cells from patients with faulty mitochondria and reverting them to induced pluripotent stem cells (iPS cells). These are reprogrammed in order to become neural progenitor cells, and are then subjected to a compound screen. This is how the researchers discovered that the already-approved drug Avanafil can reverse some of the cellular imbalances caused by a certain mitochondrial defect and they are now considering moving to clinical trials.
According to the researchers, the identified substance may work in only one particular patient or in a broader patient population. In either case, the approach makes it easy to screen thousands of drugs that have already been approved by the Food and Drug Administration (FDA). Even if the mitochondrial disease is extremely rare, the drug discovery platform can be applied to a range of conditions that lack effective model systems.
Source: Max Delbrück Center for Molecular Medicine (MDC)

Image: Gizem Inak, Prigione Team, MDC
InnovationCeramic Additive Manufacturing for Personalized Medical Products
Ceramic materials are essential for medical products, and additive manufacturing can open up new opportunities for extremely complex geometries and new material combinations. The aim of the cerAMfacturing project, which is funded by the European Commission, is the development of new ceramic multi-material additive manufacturing methods. Personalized medical products, such as spinal and knee implants, infrared heaters for supporting healing processes or curing pain, as well as grippers for minimally invasive surgery will be manufactured starting with the patient-specific physical dimensions and ending with components validated under the specific conditions.

cerAMfacturing can help patients and surgeons by lowering costs and waiting time. Production times can be reduced by at least 50 percent. Lower production costs due to tool-free production will reduce the price of medical products. Moreover, the components will be tailored to the physical dimensions of a patient or to the needs of the surgeon. Thus, a patient will have less pain and an increased quality of life. The surgeon will have better working conditions with improved surgical instruments, which in turn will be beneficial for the patient. 

BionaticInterview with Prof. Dr. med. Nisar Peter Malek, Full Professor and Managing Director at the University Hospital Tübingen, Department of Internal Medicine I
Prof. Dr. med. Nisar Peter Malek's clinical work focuses primarily on the treatment of malignant diseases of the gastrointestinal tract and liver, as well as therapy for patients with chronic liver diseases. He is a full professor and the managing director at the University Hospital Tübingen, Department of Internal Medicine I and the Chairman of the Center for Personalised Medicine at the University of Tübingen.

The focus of his scientific work is decoding cell division mechanisms, with the goal of identifying new substances for treating tumor diseases. Professor Malek was honored with the AIO Science Award in 2008 and the Johann Georg Zimmermann Prize for Cancer Research in 2009.

In this interview with the GCRI, Prof. Dr. Malek discusses future developments in personalized medicine and the role that the University Hospital Tübingen plays for this development. He describes how the Center for Personalised Medicine tries to overcome challenge of introducing cutting-edge technologies into clinical trials, and whether computing and big data analysis are necessary to make personalized medicine a success. To read the full interview, click here.
Source & Image: University Hospital Tübingen

TestSectionInnovation: TissUse Multi-Organ-Chip Platform
TissUse, a Berlin-based, vibrant growth company, has developed a unique "Multi-Organ-Chip" platform that, for the first time, provides pre-clinical insight at the systemic level using human tissue. The platform consists of a miniaturized construct that simulates the activity of multiple human organs in their true physiological context. The platform has been successfully applied in several different academic and industrial research projects.

The Multi-Organ-Chip technology has made it possible until now to replicate up to four human organs, scaled down 100,000 times, from cell tissue on a microscope slide. The organ compartments are connected to each other with a system similar to blood vessels. Micro valves replicate the heart and the cell structures react to administered substances just like a human organism.

Experiments for testing new drugs, cosmetic ingredients, and chemicals thereby do not need animal testing anymore and developers as well as regulatory authorities can test how humans react to specific substances over longer periods of time. The use of human cells also allows the results to be transferred more easily than data from animal testing.

The next generation of MOC design at TissUse, a Human-on-a-Chip, will increase the number of interconnected organs toward acceptable organismal complexity. This number of organs is supposed to efficiently provide human organismal homeostasis and be sufficiently flexible for diverse disease modelling, an approach that could revolutionize drug development.
Source & Image: TissUse