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.

Prof. Roger Tsien Honoured with Max Delbrueck Medal

He developed indispensable tools to study basic mechanisms in living cells

„For his outstanding contributions to molecular biology“ including the development of „a spectrum of novel optical methods which allow to elucidate basic mechanisms of life in intact cell“ the American biochemist and pharmacologist, Professor Roger Y. Tsien from Howard Hughes Medical Institute and the University of California San Diego (USA), has been awarded the prestigious Max Delbrück Medal in Berlin (Germany) today. „By a combination of synthetic organic chemistry, physical chemistry and molecular biology he advanced our understanding of the function of calcium ions and protein/protein interaction in celluar signalling cascades. Professor Tsien supplied indispensable tools for the investigation of cellular processes in life and disease“, according to the award citation. After the ceremony Dr. Tsien delivered his Berlin Lecture on Molecular Medicine. His topic was „Imaging Signal Transduction and Protein Sociology“.

A Protein as Fountain of Youth?

Clinical Researchers Detect Function of Protein INDY

Caloric restriction is the only known means of extending life span in mammals, including humans. This is also the case for the fruit fly Drosophila. Although the mechanism by which caloric restriction extends life span is not yet understood, researchers assume that it is likely to include alterations in energy utilization. Two years ago, Blanka Rogina and Stephen L. Helfand from the University of Connecticut Health Center (Farmington/USA) discovered a gene, which doubles the average life span of fruit flies when mutated without a loss of fertility or physical activity. The analyses of data from gene banks gave them the hint, that the gene might be involved in energy balancing. Therefore, they named the gene „I am not dead yet“ (Indy), which is somewhat macabre. Now Felix Knauf from the Franz Volhard Clinic for Cardiovascular Diseases (Charité, Medical School of Humboldt-University of Berlin/Helios Kliniken) and the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch in Germany and Stephen L. Helfand have been able to detect the function of Indy. Together with Peter S. Aronson from Yale University (New Haven, Connecticut/USA) and Blanka Rogina they were able to demonstrate that Indy`s product, the protein INDY, functions as a transporter of nutrients important for normal metabolism. Their research has now been published in the renowned American Journal Proceedings of the National Academy of Sciences (PNAS, October 29, Vol. 99, No. 22, 2002, online, http://pnas. org/cgi/doi/10.1073/pnas.222531899)*

MDC Researchers Detect Mechanism by which Human Papillomavirus Type 18 Triggers Cervical Cancer - Second most Common Cancer in Women

More than 500,000 women are diagnosed with cervical cancer each year and almost 200,000 die from it. Next to breast cancer it is the second most common malignancy in women. Human papilloma viruses (HPV), usually harmless viruses which cause warts, play a central role in the onset of cervical cancer. HPV types 16 and 18 are two representatives of the high risk human papillomaviruses which cause cervical cancer. Dr. Edgar Grinstein and Dr. Hans-Dieter Royer (Max Delbrück Center for Molecular Medicine, MDC, Berlin-Buch and Heinrich Heine University Düsseldorf, Germany) have been able to show how a healthy cell is transformed into a tumour cell after becoming infected with HPV 18. Their findings which are the result of a collaboration with researchers from the University Amsterdam, The Netherlands, the German Cancer Research Center, Heidelberg, and the Charité, Campus Mitte, Medical School of the Humboldt University of Berlin/Germany have just been published in the renowned American Journal of Experimental Medicine (Volume 196, Number 8, October 21, 2002, 1-13, http://www.jem.org/cgi/doi/10.1084/jem.20011053)*

Prof. Arya M. Sharma to accept Chair at Canadian University

Prof. Arya M. Sharma, an internationally renowned specialist in the research and treatment of obesity and hypertension from Berlin-Buch (Germany) has accepted a “Canada Research Chair for Cardiovascular Obesity Research and Management“ at McMaster University in Hamilton/Ontario. Prof. Sharma will leave the Franz-Volhard-Clinic for Cardiovascular Diseases of the Charité Medical School of Humboldt University of Berlin and the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch this Autumn.

Researchers from MDC and DHZB Receive Awards

Therapy for chronic heart muscle disease developed – Extra-corporal blood purification filters damaging autoantibodies out of the blood.

For the development of a blood purification therapy to treat chronic heart muscle disease (dilated cardiomyopathy, DCM), Dr. Gerd Wallukat from the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch and Dr. Johannes Müller from the German Heart Institute Berlin have been awarded the “Apheresis Innovation Prize of the German Working Group for Clinical Nephrology“. The two Berlin scientists share the prize, which is endowed with 8000 euros, with Dr. Markus Suckfüll from the Klinikum Großhadern in Munich, who received the award for his research on a therapy for acute hearing loss.The prize, which is awarded every two years, was presented to the three research scientists on Monday, the 30th September 2002, within the framework of the 33rd Congress of Nephrology in Düsseldorf.

International Conference on Structural Genomics

International Structural Genomics Organisation (ISGO)

Thursday, October 10 – Sunday, October 13, 2002

Max Delbrück Communications Center (MDC.C)

Diversin - MDC researchers discover a new gene

A regulator of a critical signal molecule in cells

A gene which plays a key role in the smooth “signal trafficking” between cells and, hence, in the development of a healthy fully functional organism, has been identified by Prof. Walter Birchmeier and his group at the Max Delbrück Center for Molecular Medicine (MDC), Berlin-Buch, a National Research Centre of the Helmholtz-Association. The gene is associated with a highly complex signaling system, the so-called Wnt pathway. It extends from the cell surface into the cell nucleus. If signal transmission via this information channel is disrupted, this can lead to construction errors and tumors. Thomas Schwarz-Romond and Prof. Birchmeier have been able to show that the gene triggers the breakdown of beta-Catenin, an important member of this signal chain, thereby preventing it from operating at the wrong time in the cell nucleus and causing local damage. They have also been able to elucidate the individual activation steps (phosphorylation) of this key breakdown process. The researchers have named this gene “Diversin” since it most likely has a number of diverse functions in the body. Their study has just been published in the research journal “Genes and Development”* (Vol. 16, No. 16, August 15, 2002; http://www.genesdev.org).

Research Report of the Max Delbrück Center published

For the first time in German and English

The Max Delbrück Center for Molecular Medicine (MDC) Berlin Buch, a member of the Helmholtz Association of National Research Centres, has published its biennial Research Report. The report, which is close on 200 pages, is published for the first time in German and English. It gives an overview of the research carried out at the MDC during the period 2000 - 2001 in the fields of cardiovascular research, cancer research, the neurosciences, genetics, bioinformatics and structural biology, cell growth and cell differentiation as well as molecular and gene therapy.

Discovery of a New Form of Familial Hypercholesterolemia

A new form of familial hypercholesterolemia involving two genes on two different chromosomes has been discovered by German and Syrian gene researchers in a Syrian family. They studied a Druze family that resides in southern Syria. The Druze are a distinct ethnic group, living in well-defined areas of the middle East, primarily in Lebanon and Syria. The family came to the attention of the researcher because 3 young members developed typical features of hypercholesterolemia, including giant tendon xanthomas. However, they showed no symptoms of atherosclerosis or myocardial infarction. Also anti-cholesterol treatment failed in these subjects. The gene analysis of 72 members from this family showed that the three affected persons had two defect genes on two different chromosomes, namely chromosom 1 and 13. The researchers have also identified the genetic defect (mutation) in this gene on chromosome 1 in this family. The new findings of Hussam Al-Kateb and Friedrich Luft (Franz Volhard Clinic for Cardiovascular Diseases (Charité, Humboldt University of Berlin and Max-Delbrück Center for Molecular Medicine, MDC, Berlin-Buch) and their colleagues from the Universities of Damaskus (Syria) and Bonn and Heidelberg has been published in the journal Circulation Research (May 17, 2002, 90).

Dr. Carmen Birchmeier awarded the Leibniz Prize

She and another eleven researchers honoured

Developmental biologist and gene researcher Dr. Carmen Birchmeier from the Max Delbrück Center for Molecular Medicine (MDC), Berlin-Buch has just won the most valuable award of the German Research Society (Deutsche Forschungsgemeinschaft, DFG), the Gottfried Wilhelm Leibniz Prize. Birchmeier and a further eleven researchers were also honoured in the Berlin-Brandenburg Academy of Sciences. Scientists who depend on equipment for their research get 1.55 million Euro (3 million German marks) each, so does Dr. Birchmeier, while scientists engaged in theoretical research receive 775,000 Euro (1.5 million German marks) each. The prize is awarded for a period of five years.

Hakai – the Destroyer

MDC Cell Biologists make New Discovery

What holds cells together and what allows them to break free of their normal environment? These questions play key roles in the development of all living organisms as well as in the development of metastases in some cancers. They have intrigued molecular and cell biologists for many years. The research group of Prof. Walter Birchmeier from the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch has been studying molecules which bind cells to one anoother like cement, the so-called adhesion molecules. The researchers have also been able to identify molecules which can “dissolve” this cell cement, turning cells into vagabonds. Now Dr. Yasuyuki Fujita and Prof. Birchmeier have discovered a new molecule which not only breaks down the cell cement but also ensures that important cell anchors are dismantled at the same time. Dr. Fujita and Prof. Birchmeier have called their molecule ”Hakai”, after the Japanese word for destruction. The MDC researchers  findings in collaboration with researchers from the Forschungsinstitut für Molekulare Pharmakologie (FMP, also in Berlin-Buch) and from the Universities of Erlangen and Cologne have just been published in the renowned research journal, Nature Cell Biology (Vol. 4, No. 2)*.

Berlin researchers discover a potential role for the complement system

two years after the first gene therapy fatality

Adenoviruses are the most common carrier systems used in gene therapy studies to transport therapeutic genes into cells in the body. However, in the USA two years ago, Jesse Gelsinger, an 18-year-old patient, died suddenly of organ failure after direct injection into his bloodstream of attenuated adenoviruses used as a “gene taxi”. The exact molecular cause of his death remains unexplained. Now, a report of a hitherto unobserved immune reaction to adenoviruses has now been published by a research team headed by Dr Günter Cichon from the Humboldt University of Berlin, at the Max Delbrück Center for Molecular Medicine (MDC), Berlin Buch, and Prof. Reinhard Burger from the Robert Koch Institute, Berlin, in the January issue of the journal “Gene Therapy” ( Vol. 8, Issue 23, 2001, pp. 1794 – 1800)*. In the laboratory, large quantities of adenoviruses as used in gene therapy triggered an unexpectedly strong activation of the so-called complement system. The complement system consists of a group of proteins which circulate in the blood and act as an initial protection system against the threat posed by infectious pathogens. In order to increase patient safety, the authors suggest that in the future the status of the complement reaction be measured by a simple test before gene therapy is administered.

Defects in Titin, the largest Human Gene, cause Chronic Congestive Heart Failure

A chronically failing human heart, inable to pump an adequate amount of blood, can be the consequence of myocardial infarctions, high blood pressure or cardiac valve disease. However, it can also occur without any obvious cause and a significant number of such cases are due to unknown gene defects. Now, Dr. Brenda Gerull and Prof. Ludwig Thierfelder (both from the Max Delbrück Center for Molecular Medicine, MDC, in Berlin-Buch and the FranzVolhard Clinic, Charité, Humboldt University, Berlin), in collaboration with researchers from Brisbane (Australia), Mannheim (Germany), and Boston (USA)* have shown that defects in the titin gene – which carries the blueprint for the largest known human protein – can lead to an inherited form of chronic congestive heart failure, a condition called familial dilated cardiomyopathy (DCM). This discovery by the MDC researchers has now been published in the prestigous journal Nature Genetics.