SIEMENS

The numbers speak for themselves. At least 200,000 people in Germany alone suffer from cardiomyopathy, an often genetically-triggered deterioration of the function of the myocardium — in short, the heart. To date, researchers have identified more than 50 genes that can cause the disease or increase its severity if they are defective. Currently available diagnostic techniques cannot definitively isolate the genetic causes of this cardiovascular disease.

Dr. Benjamin Meder, a physician at Heidelberg University Hospital, believes this represents a huge challenge. “In general, modern diagnostic methods, such as magnetic resonance tomography, can only detect weaknesses in myocardial performance,” he says. “In most cases the precise cause of the condition can not be identified.”

Like most other illnesses, cardiomyopathy can have many causes. “It could be genetic, but it doesn’t have to be,” Meder explains. In fact, the symptoms can also be caused by toxic damage, a virus infection or a circulatory disorder. The problem is that knowing the precise cause is very important when choosing treatments and making medical prognoses. “Some gene alterations can be very dangerous to a patient,” says Meder.

With this in mind, in 2011 scientists from Heidelberg University teamed up with colleagues from Siemens Corporate Technology (CT) in Princeton, New Jersey, to develop new software that not only analyzes and manages the huge amount of data generated by genetic tests but also presents it to physicians in a very clear manner. “Here we used tried and tested software as a basis and then recombined the software components in an intelligent way,” says Dr. Andreas Keller, a researcher from the Chief Technology Office of Siemens’ Healthcare Sector.

Looking for RNA. New techniques now being developed could be used to quickly and reliably diagnose a heart attack. Until recently, the common practice for this was to analyze a patient’s blood for proteins that are released by the heart muscle during a heart attack. Here too, the presence of such proteins can have many different causes, which can make it very difficult to quickly differentiate between a heart attack and a heart muscle infection, for example. A more rapid and possibly better way to diagnose a heart attack would be to look for special micro-RNAs — i.e. ribonucleic acids — in the patient’s blood or serum. So-called “micro-RNAs” have been found to play a key role in the complex gene regulation network. This new diagnostic field is very promising, which is why Heidelberg University and Siemens are collaborating to assemble key genetic, clinical, and technological information in this area. “Micro-RNAs enter the bloodstream via two different mechanisms when a heart attack occurs,” says Meder. They are either released when heart tissue dies, or else there is a change in the micro-RNAs in cell types such as leucocytes and thrombocytes that occurs as a reaction to a traumatic event. It is basically possible to identify such markers for diagnostic purposes today, but the laboratory techniques required for this are time-consuming and expensive. Nonetheless, CT researchers in Erlangen have taken up the challenge. Within the framework of Siemens’ “Translational Biotechnology” lighthouse project, they are examining whether a type of “lab-on-a-chip” platform could be developed that would allow such tests to be conducted simply and quickly. The researchers are focusing mainly on better methods for diagnosing heart attacks on the basis of micro-RNAs.

Genetic First Aid. An initial demonstration unit for improved genetic analysis of heart muscle weakness (dilated cardiomyopathy) was recently completed (September 2012) at Heidelberg University Hospital. “We hope to see initial results soon, as the cardiologists in Heidelberg already have data sets for around one thousand patients,” Keller explains. He adds that another 150 data sets will be added to the collection each year, which will provide doctors with an increasingly solid foundation for future studies.

“Of course, the challenge is also to make sure that a physician isn’t just given simple lab results, as was previously the case,” Keller says. Instead, he or she will be issued gigabytes of information on each patient. That won’t be a problem, however, given the fact that Siemens has many years of experience and expertise in evaluating large amounts of data. “Our strength here is the ability to extract clinical information that doctors can understand,” says Keller.

"Our initial goal for the demonstration unit is to prove that the sequence data we collect corresponds to clinical expectations," explains Dr. Emil Wirsz, a Siemens researcher from CT in Erlangen who heads the Translational Biotechnology lighthouse project. “Our primary focus is to improve the diagnosis of cardiomyopathy, but our systems can also be modified, which means we can use them to detect other cardiovascular diseases — and even apply them to completely different areas, such as the early detection of cancer."

Wirsz says the scientists started with cardiological disorders because they’re easier to manage than cancer-related diseases. The latter are more complex, of course. “But that’s all right, because we can learn from the cardiology applications and then transfer the knowledge we gain to other areas,” he says. To this end, Siemens Healthcare is planning partnerships with several cancer research organizations. “We’ll probably start with tumor diagnosis in children,” says Keller. That’s because the influence of genetic predisposition in such cases is generally very high. It may be possible over the medium term to examine the blood of cancer patients in a targeted manner designed to identify genetic defects, and then use the results to draw up an optimal treatment approach. The software developed by Siemens will gradually be expanded to accommodate this approach, says Keller.

Although the goal of the Erlangen and Heidelberg research programs is to ultimately revolutionize diagnostic methods, they are already thinking about possibilities for improving individualized disease prediction. “It’s conceivable that we’ll be able to affordably conduct complete genome sequences in the near future,” says Wirsz. This could allow risk factors to be identified for a variety of conditions, such as many heart diseases, cancers, and Alzheimer’s disease.

Naturally, with so much sensitive information potentially flowing from tomorrow’s genomic tests, the issue of data security will become increasingly important. “We are working on multiple levels to ensure that patient data will remain accessible only to authorized individuals,” says Keller. That will be crucial as data is increasingly stored on external servers in the cloud.

Personalized Medicine. Siemens researchers are also taking a close look at the future field of pharmacogenomics, which involves medical treatments tailored to a patient’s individual genetic profile. This issue is very important because it’s becoming more and more difficult to develop new medications that are effective for large segments of the population yet that have few side effects. The pharmaceutical industry needs to invest billions if such blockbuster drugs are to be created. Up until now, regulatory organizations have refused to approve medications that only help 20 percent of patients on average. Now, however, we know that genetic makeup often determines whether or not a certain drug will work on a patient — and a susceptibility to specific side effects is often inherited as well. The new trend here is companion diagnostics — tests that can be used to determine whether a treatment in a specific case will lead to success, and thus to indicate whether the drug in question should be approved for use with certain patient groups. “This is exactly the situation in which our software can be used as well. In other words, it might help personalized medicine achieve a big breakthrough,” says Wirsz.