No 14/December 2, 2002
Extra-corporal blood purification filters damaging auto-antibodies out of the blood - Promising results from the first clinical trial with this therapy for chronic heart muscle disease
The cardiac performance of patients suffering from chronic
heart muscle disease (dilated cardiomyopathy, DCM) has been shown to improve
after they underwent a therapy filtering specific auto-antibodies damaging the
heart muscle out of the blood. Dr. Gerd Wallukat from the Max Delbrück Center
for Molecular Medicine (MDC) Berlin-Buch, Dr. Johannes Müller and Professor
Roland Hetzer from the German Heart Institute (Deutsches Herzzentrum) Berlin
have published the results from the first clinical trial of this therapy in the
latest issue of the New New England Journal of Medicine („Specific Removal of
beta-1 Adrenergic Autoantibodies from Patients with Idiopathic Dilated
Cardiomyopathy“, Vol. 347, 28. November 2002, No. 22). Using a novel adsorber,
developed by Dr. Wallukat and Dr. Müller in conjunction with medical
technologists of the biotech company Affina Immuntechnik GmbH (Berlin), they
filtered specific auto-antibodies targeted at beta1-adrenergic receptors out of
the blood of the patients – similar to dialysis with renal patients. Auto-antibody
removal was performed on five consecutive days for 3 – 4 hours each day. Even
one year later, the level of auto-antibodies in the blood of the patients
remained „very low”. „The first application of this specific immune adsorption
system within a clinical study has led to a considerable improvement in the
heart function of the patients treated,” Dr. Müller points out. „The specific
immune adsorption is also free of side effects, the heart surgeon said. The
first positive results are now to be investigated further in multi-center
studies in a larger number of patients.
More than 280,000 people in Germany alone suffer from chronic dilated cardiomyopathy (DCM). In this disease, the pumping capability of the heart is reduced, and the heart muscle becomes enlarged (dilation – expansion) to compensate for the reduction in efficiency. Those affected by the disease are considerably restricted in their physical capability. Up to now this disease has been treated with drugs which have provided only short-term benefits. In the most severe cases, patients may require a heart transplant or the insertion of a pump.
It is not clear yet whether these auto-antibodies play a crucial role in the onset of this serious heart disease in humans, Dr. Wallukat, Dr. Müller and Professor Hetzer point out in their report. However, this is the case in animals. The causes of this serious heart disease are varied and many. In some cases the cause is genetic, i.e. familial.
In about 80 percent of patients with dilated cardiomyopathy, Dr. Wallukat was able to detect auto-antibodies which attack the beta1-adrenergic (beta1-AR) receptors of heart muscle cells. It is unclear, however, why the body’s own immune system is no longer able to distinguish between „foreign” and „self”. Via beta-adrenergic receptors, the messengers (hormones) noradrenaline and adrenaline regulate the heart rate and pump function (contractibility). „The auto-antibodies activate beta1-adrenergic receptors, interfering with the calcium regulation of the cells, thereby altering their function,“ explains the cell biologist. Building on these fundamental investigations at the MDC, Dr. Wallukat and Dr. Müller, together with medical technologists of the biotech company Affina Immuntechnik GmbH (Berlin), have developed an adsorber which filters these specific auto-antibodies targeted at beta1-adrenergic receptors out of the blood of the patients.
In addition, there is a second form of this treatment, which has also been recently developed, but which removes non-specific auto-antibodies by filtration. However, according to Dr. Müller, „in non-specific immune adsorption side effects can arise in individual cases, leading to a premature termination of treatment”. To date, more than 100 patients suffering from chronic heart muscle disease have been treated at the German Heart Institute Berlin with these two techniques. The first positive results are now to be investigated further in multi-center studies in a larger number of patients.
Recently, Dr. Wallukat and Dr. Müller were awarded the „Apheresis Innovation Prize of the German Working Group for Clinical Nephrology“ for their development of this novel blood purification therapy to treat chronic heart muscle disease.
Barbara Bachtler
Press and Public Affairs
Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch
Robert-Rössle-Straße 10; 13125 Berlin; Germany
Phone: +49 (0) 30 94 06 - 38 96
Fax: +49 (0) 30 94 06 - 38 33
e-mail: presse@mdc-berlin.de
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