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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 34 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 (030
94 06 — 38 33
e‑mail: presse@​mdc-​berlin.​de
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