Story

The heart of the matter

Dr Peter Kolkhof (left) and Dr Johannes-Peter Stasch, for example, are developing innovative therapeutic approaches and new active ingredients that help combat heart failure.

Essential for life: The heart has only one function, and that decides between life and death. It has to pump blood through the pulmonary circulation and the rest of the body to ensure that all the organs are perfused. Yet a strong heart and intact blood vessels can’t be taken for granted. Every year millions of people all over the world die as a result of diseases affecting the cardiovascular system. A large number of researchers and developers at Bayer HealthCare Pharmaceuticals are working on ways of managing these diseases.

Dr. Lars Bärfacker is a chemist and a creative person. He’s always looking for things that haven’t been seen before – in the same way as an architect or a designer. Shapes and structures are very important in Bärfacker’s work too. A chemist lives in the world of molecules. These are tiny structures that no-one can see with the naked eye. It’s really only scientists who are able to imagine what they look like and how they can be made. Although numerous compounds have already been described in the chemical literature, scientists like Bärfacker constantly create new substances with the aim of uniting all the decisive pharmaceutical properties in a single structure.

Click here for more about researchers and developers at Bayer HealthCare Pharmaceuticals

Previous Image Next ImageImage 1 of 2

The engine: The heart (shown here as a color negative) pumps blood throughout the body. The coronary arteries ensure that it is also well supplied with blood.

What drives them is the search for the compound which is best suited to a defined task. Bärfacker, for example, spent many years looking for a substance to treat heart failure. The therapy of this disease is one of the main areas of research atBayer HealthCare Pharmaceuticals. In his mind’s eye, Bärfacker designed one molecule after another, hoping every time that it would bring him closer to his goal. At the same time he had to develop a synthesis path so that his colleagues in the laboratory could produce a few milligrams of the substance. Such tiny amounts provided biologist Dr. Peter Kolkhof with enough material to carry out the first activity tests on cell cultures, for example, in his pharmacology laboratory in Wuppertal. Bärfacker needed the results of these tests so that he and his team could continue optimizing the chemistry of the molecule.

Behind every new pharmaceutical active substance is a large project team which includes researchers like chemist Bärfacker and biologist Kolkhof. One provides a continuous stream of new substances, the other tests them to see whether and how well they work. Both scientists basically have a single goal: to find a key which fits into a unique lock. Any other result would mean that the possibility of the compound having adverse effects could not be excluded. The objective in the therapy of heart failure is to find a way of influencing the action of the hormone aldosterone, which occurs naturally in the body. “We had to make sure that we weren’t shutting down testosterone at the same time,” Kolkhof says. An anti- aldosterone drug already on the market had caused the painful development of breasts in men, so this was an exclusion criterion in the search for a new active substance.

The "tremendous motivation" of treating diseases better

Zoom image

The chemist: Dr. Lars Bärfacker creates new substances which hopefully have the potential to become new drugs. The results of biological testing help him to optimize his work.

“Sometimes we get molecules which work beautifully,” Kolkhof says, “but then we find something else about them that isn’t good.” Either the substance doesn’t work exactly where it should in the body. Or it is broken down too quickly. Or a toxic side effect is discovered which nobody had thought of beforehand. There are many reasons for setbacks in drug discovery. Some of the molecules designed on paper fail to meet expectations in critical experiments. Then it’s back to square one. It’s an up-and-down process which, in the case of the aldosterone inhibitor, took over four years and thousands of substances – with “a lot of setbacks and rare moments of happiness.” But Bärfacker also talks about the “tremendous motivation” provided by the prospect of being able to treat diseases more effectively or even save lives one day. B AY 94-8862 looked like bringing the researchers closer to their goal. The compound was thought to be promising enough to move into clinical development – and interesting enough for Dr. Silvia Lentini, a specialist in internal medicine. She is a project manager in Clinical Pharmacology, and was an important addition to the team working with Bärfacker and Kolkhof. Every drug-development project needs an expert to plan and initiate a program of clinical pharmacology trials. “We are now investigating our aldosterone inhibitor in healthy volunteers,” Lentini explains. The program will also focus on patients with heart failure who are suffering from kidney failure. Kidney failure is common in these patients and makes their prognosis less favorable. However, the use of most of the registered active substances is restricted in patients with kidney failure. Yet these patients need to be treated too. “We hope that by developing an improved aldosterone inhibitor like BAY 94-8862 we will be able to help precisely these patients at an early stage,” Lentini explains.

Click here for more about cardiovascular diseases and innovative therapeutic options

Zoom image

The biologist: Dr. Peter Kolkhof carries out initial tests with drug candidates to see if they could be effective in heart failure, for example. He gets the test substances from the chemist.

Heart failure is the term used to describe the progressive inability of the organ to pump sufficient blood round the body. An estimated 20 million people worldwide suffer from this condition, often as a consequence of other disorders such as high blood pressure or a heart attack. Water retention and shortness of breath on physical exertion are typical features associated with a weak heart. At an advanced stage of the disease even walking becomes a burden. “Fifty percent of people diagnosed with serious heart failure have a life expectancy of five years at most,” Kolkhof says. Many chronically overloaded hearts typically develop an increased amount of connective tissue. The walls of the organ thicken, which in turn reduces the volume of the chambers of the heart and makes the entire muscle less flexible. This development is driven by aldosterone. The body actually secretes this hormone as a way of protecting itself against the loss of pumping action, but in the longer term it only makes the condition worse. The objective of the researchers at Bayer HealthCare Pharmaceuticals was therefore to block the action of aldosterone. “There is initial evidence from preclinical trials that inhibiting this hormone not only improves the excretion of water but also allows the rigid heart muscle to regain its flexibility,” Kolkhof says. This means that the changes to the heart would not only be halted but maybe even reversed.

Apart from Kolkhof and Bärfacker, other researchers at the company are also working on the heart. Some of them are in fact also working on heart failure, but are pursuing a different approach. They are currently investigating a substance designed to reduce the resistance in the pulmonary vessels against which the heart has to pump. This substance is already undergoing clinical trials in patients with acute heart failure.

New therapeutic options for pulmonary hypertension

Dr. Gerrit Weimann is working on an other condition which also puts a tremendous strain on the heart. The doctor, also a Bayer HealthCare Pharmaceuticals scientist, is investigating therapeutic options for pulmonary hypertension. “This condition develops when the blood vessels in this organ become narrow and hardened, as this prevents the uptake of oxygen,” he explains. This rapidly leads to shortness of breath and, in the worst case, to permanent overloading of the heart. The reason is that the constant lack of oxygen forces the heart to pump harder to push more blood into the lungs. Pulmonary hypertension has been treated for years with drugs such as inhaled prostacyclins. Bayer HealthCare Pharmaceuticals markets a product in this category. The company is now taking a completely different approach with its new active substance riociguat so that patients no longer need to inhale. Tablets will make it easier for them to use the product. Riociguat belongs to a new class of substances known as sGC stimulators. These were discovered by Professor Johannes-Peter Stasch, a chemist and pharmacist, who hopes that it will soon be possible to offer the first effective and well-tolerated medication in tablet form. “The initial clinical trials with patients are producing promising results,” he says. In addition, preclinical studies suggest that “riociguat not only improves the symptoms of pulmonary hypertension but can also slow the progression of the disease.”

Click here for more about cardiovascular prevention and prophylaxis

Zoom image

The physician: Dr. Silvia Lentini is responsible for the first clinical trials which Bayer HealthCare Pharmaceuticals carries out with potential drugs for cardiological indications.

Blocked blood vessels can also lead to a stroke or a heart attack if the supply of blood to the brain or heart is interrupted. Under normal circumstances the heart of a healthy person pumps about six liters of blood through the body’s blood vessels every minute. So somebody who has reached the age of 70 has pumped around 200 million liters of blood through his arteries in that time. A stroke happens when an inadequate flow of blood supplies the brain with too little oxygen. The consequences are well documented: impaired speech or vision, paralysis or impaired consciousness. If the heart doesn’t get enough oxygen and suffers an infarction, rhythm disorders, heart failure and inflammation of the heart muscle may result. Often, though, the outcome is death. This is why it is so important to stop these events from happening in the first place – with a healthy lifestyle and preventative medication. This applies particularly to people who have a higher risk of developing narrowing of the blood vessels or blood clots. Here, too, Bayer products have long been playing a major role.

Many patients take a low-dose formulation of Aspirin, for example, to prevent these problems. This version of a medicine which is more than 110 years old was developed specially for long-term administration. “The active substance, acetylsalicylic acid, is used to prevent the platelets in the blood from clumping together,” explains Brigitte Havertz, a pharmacist who works for Bayer HealthCare Deutschland. “This keeps the blood flowing even when damaged vessel walls “mistakenly encourage the platelets to stick together.”

Around 70 percent of high-risk patients have been receiving insufficient treatment or none at all

People with atrial fibrillation are also at risk of their blood coagulating when it shouldn’t. In this disorder of cardiac rhythm the heart beats faster but less effectively. This means that blood gets left behind in certain parts of the atrium, the upper chamber of the heart. The risk of a blood clot, or thrombus, forming is increased because the blood is not moving. If a thrombus wanders from the atrium into the left ventricle, through the aorta and the carotid artery into the brain, the vessels there can become blocked and trigger a stroke.

It is estimated that one in five of these strokes, known as ischemic strokes, is caused by atrial fibrillation. Moreover, this type of stroke leads to particularly severe neurological impairment. “Up to now, around 70 percent of high-risk patients have been receiving insufficient treatment or none at all,” explains Dr. Frank Misselwitz, Head of Global Clinical Development in the Cardiovascular and Coagulation therapeutic area at Bayer HealthCare Pharmaceuticals. One of the reasons for this is that the standard therapies currently available are difficult to dose because of their many interactions and are associated with an elevated risk of bleeding. The pharmaceutical company hopes to fill this therapeutic gap with rivaroxaban in the future. This active substance is intended to be convenient to take in tablet form, which would make it easy to dose. Rivaroxaban is already available in many countries for the prevention of thrombosis following elective hip or knee replacement surgery. Clinical studies are currently investigating the suitability of this substance for the prevention of stroke in patients with atrial fibrillation. “We expect to have the results before the end of this year,” Misselwitz confirms. And as he says these words, his hope and pleasure are palpable. Even the many setbacks and periods with little progress play a secondary role here. It’s the same for Bärfacker, Kolkhof, Lentini and all the other people working in Research and Development. They are all committed to reaching one major goal. They hope that their work will help to cure diseases or to improve the quality of life of patients worldwide.

Interview with Director of Cardiology Professor Erland Erdmann

Professor Erland Erdmann, Director of Cardiology at Cologne University Hospital.

Zoom image

Professor Erland Erdmann,Director of Cardiology at Cologne University Hospital

Professor Erdmann, do heart patients fare better nowadays?

Yes - thanks to medical progress. Stents to support the vessels are now inserted quickly and routinely. Drugs capable of stopping platelets clumping together are more powerful, and there are fewer infarctions because people with symptoms seek medical advice earlier and can be treated more effectively. Heart patients who look after themselves live longer nowadays.

Where would you like to see new developments?

It would be an enormous advantage for the many patients with atrial fibrillation or artificial heart valves if they could simply take one tablet a day, without needing to have their coagulation status checked all the time or to watch what they eat. For patients with heart failure we need diuretics which don’t disrupt the electrolyte balance and drugs which increase the contractile force of the heart muscle without diminishing life expectancy.

How long can an intact heart live in theory?

I’ve had a 99-year-old patient with a completely normal heart. I reckon that people who take good care of their hearts could live to be 130.

When help comes too late

Zoom image

Emergency: When the heart stops, every second counts.

Roughly 30 percent of all deaths worldwide are the result of cardiovascular diseases. The figure in 2005 was about 17.5 million. The World Health Organization (WHO) estimates that it could rise to 20 million by 2015.
According to the WHO, in 2005 7.6 million people died as a result of coronary artery disease leading to a heart attack or heart failure.
The WHO reckons that some 80 percent of cardiovascular conditions are the result of lifestyle factors such as a poor diet, too little physical activity and smoking.

Women’s hearts are different. Studies have shown that women are often treated later – and therefore less successfully – if they have a heart attack. One of the reasons for this is that the symptoms of an infarction are often different in women and less obvious than in men. For example, they may not experience the chest pain typically associated with a heart attack.

The heart of the matter

Click here for more about researchers and developers at Bayer HealthCare Pharmaceuticals

Click here for more about cardiovascular diseases and innovative therapeutic options

Click here for more about cardiovascular prevention and prophylaxis

Interview with Director of Cardiology Professor Erland Erdmann

When help comes too late

Special Interest

Print page

Search

Podcast

Bayer Magazine

Links