December 22, 2003

Try as we may to suppress memories of highly stressful experiences, they nevertheless come back to bother us — even causing attacks of intense fear or other undesirable behavioral impairments.

Now, a team of scientists has found that a gene-based approach pioneered at Hebrew Univeristy offers promise for development of a treatment that can suppress these reactions, while not impairing memory itself.

In an article appearing as the cover story in the current issue of Molecular Psychiatry, a team of researchers from the Silberman Institute of Life Sciences at the Hebrew University of Jerusalem and the Max Planck Institute for Experimental Medicine in Goettingen, Germany, describe their work with mice that were subjected to stressful conditions.

“We know that we remember more profoundly experiences that are associated with time and place when we underwent trauma,” explained Prof. Hermona Soreq of Hebrew University in an interview with Israel 21c. Soreq’s research drove the study, and who is about to publish a book on stress responses.

The challenge, Soreq explained, has been to identify the protein behind our stress responses.

Soreq’s team did so by discovering that stress induces a change in the expression of the acetylcholinesterase gene. Under normal circumstances, this gene produces a vital protein that adheres to neuronal synapses (the interaction sites through which nerve cells communicate with each other). Following stress, however, the same gene produces large quantities of a protein with modified properties that results in heightened electrical signals in the nerve cells communicating through these synapses. The effect is to create reactions of extreme fright or immobilizing shock.

“It is this protein that causes the memory to be inscribed, etched so deeply in us,” Soreq said.
Later encounter with a context which arouses those stressful memories — which might be an object, a sound, an image or other form of association — can set off that same neuronal reaction. Often, this reaction can have serious consequences, such as chronic fatigue or personality disorders, including post- traumatic stress disorder (PTSD). In the U.S., it is estimated that more than 15 million people a year are identified with PTSD or other anxiety disorders.

The research team at the Hebrew University and in Germany and Britain has succeeded — based on more than 10 years of research in Prof. Soreq?s Jerusalem laboratory — in developing an “antisense” agent that acts to neutralize the process whereby the modified protein is produced, thereby preventing the extreme reaction associated with traumatic memory-inducing stimuli.

The experiments were performed with mice, Prof. Soreq explained, and the team was able to minimize — if not to block completely — their stress responses by injecting them with the antisense agent.

The researchers from the Hebrew University involved in the project were Prof. Soreq, who heads the Eric Roland Center for Neurodegenerative Diseases, and Dr. Binyamin Hochner and graduate students Noa Farchi and Ella H. Sklan. Also participating was Dr. Shai Shoham of Herzog Hospital in Jerusalem. From the Max Planck Institute, the participants are Prof. Joachim Spiess, Dr. Thomas Blank and Ph.D. students Ingrid Nijholt and Min-Jeong Kye. Involved with the work also were Birgit Verbeure and David Owen of the Medical Research Council Laboratory of Molecular Biology, Cambridge, England.

The object of the research is not to erase memory, emphasizes Prof. Soreq — since memory of dangerous situations or circumstances can be beneficial for survival — but rather to develop a drug that would block the harmful reactions of those suffering from recurring stress symptoms due to lingering memories of past traumatic experiences. Until now there has been no drug to treat the core of the post-stress problem, but rather only its symptoms.

Working towards creating a commercial medicinal product based on the research is Ester Neurosciences, a startup company in Tel Aviv, with backing from the Medica Venture Capital Fund, by agreement with the Yissum Research Development Company of the Hebrew University.

While they are still far from developing a drug that can be tested and used on human beings, the identification of the protein and the successful experiments with mice “have brought us a great deal closer,” said Soreq.

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Jason Harris

Jason Harris

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