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PROF. AVI ORR-URTREGER, director of Ichilov’s Genetics Institute and professor of Pediatrics and Genetics at Tel Aviv University..(Photo by: ICHILOV SPOKESPERSON'S OFFICE)
Searching for a cure for Parkinson’s at Ichilov
By ALAN ROSENBAUM
11/01/2018
For decades, professors Nir Giladi and Avi Orr-Urtreger of Tel Aviv’s Sourasky Medical Center have harbored a seemingly impossible medical dream.
For decades, professors Nir Giladi and Avi Orr-Urtreger of Tel Aviv’s Sourasky Medical Center have harbored a seemingly impossible medical dream. They have been on a mission to prevent the onset of Parkinson’s disease and to arrest the progress of the disease for those who have contracted it. Now, according to the pair, this goal is finally within reach.

Giladi, chairman of the hospital’s Neurological Institute and professor of Neurology at Tel Aviv University, has been researching the causes of Parkinson’s since 1990. Orr-Urtreger, director of the Medical Center’s Genetics Institute, and professor of Pediatrics and Genetics at Tel Aviv University, who holds both MD and PhD degrees and who conducted research in medical genetics at Houston’s Baylor College of Medicine, joined forces 12 years ago with Giladi. In the course of their research, they made a startling discovery, which has turned Israel into one of the world’s leading areas for the study of Parkinson’s disease.
Parkinson’s disease, a chronic, degenerative disease of the central nervous system, affects the parts of the brain that are associated with movement and balance. Symptoms can include tremors or shaking of the hand or other limbs while at rest, as well as rigidity and increased tone in the body’s muscles. Body movements are slowed, and patients can have difficulty maintaining balance. Currently, there is no cure, and treatments are directed at reducing symptoms.

Giladi and Orr-Urtreger discovered that there is an association between Parkinson’s and a gene mutation found in Ashkenazi Jews. Ashkenazi Jewry is considered genetically homogeneous, because they have stayed together as a group, marrying within, and remaining as a separate group for more than 1,000 years. As a result, explains Orr-Urtreger, “Ashkenazi Jews are an excellent model to learn genetics.”

Giladi says that due to the large number of Jews of Ashkenazi descent in Israel, “there are many more Parkinson’s patients in Israel than in other Western countries. Until recently, Parkinson’s was not considered a ‘Jewish’ disease. We are beginning to look at it as a Jewish disease.” There are approximately 25,000 Parkinson’s patients in Israel today.

GILADI AND Orr-Urtreger succeeded in establishing the world’s largest cohort of patients with genetic Parkinson’s, due to known mutations in the LRRK2 and the GBA genes, in the general Ashkenazi sector of the population in Israel. “There are about 250,000 people in Israel that carry this genetic mutation as a possible cause for Parkinson’s,” says Giladi. “This makes Israel a very interesting place for research, and makes it possible to understand how the disease develops.” Adds Orr-Urtreger, “What we learn here can be for the benefit of the entire world.”

A staggering 8.5% of all Ashkenazi Jews carry a mutation in one of the two genes, creating a group of 250,000 people in Israel who are at risk of developing genetic Parkinson’s. The mutated gene is passed from generation to generation, resulting in a great number of Parkinson’s disease cases within an extended family.

Currently about 2,500 Jews of Ashkenazi descent have been examined and genetically categorized at Sourasky Tel Aviv Medical Center, also known as Ichilov, which has resulted in the diagnosis of over 400 patients with genetic Parkinson’s, by far the highest number in a single center worldwide. Upon recognizing a mutation-associated Parkinson’s patient, doctors contact first-degree relatives of those patients, who are at high risk for developing the disease. Over the past decade, 600 at-risk relatives, all over the age of 40, have been examined and have been followed under research protocols; 15 of the at-risk relatives were eventually diagnosed with the disease.

The unique group of Parkinson’s subjects has provided researchers with the ability to detect unique clinical and genetic markers of Parkinson’s as well as to better characterize the years prior to onset of the disease. In addition, it has enabled researchers to understand and discover genetic modifiers that play a major role in the multi-factorial equation of who will develop Parkinson’s, of what type and when. The genetics-based approach of Giladi and Orr-Urtreger enables a more personalized approach to treating patients with Parkinson’s based on their genetic background.

Giladi explains, “Our research is built on cooperation between the patients who are sick, their families and the researchers. We need to check healthy people to predict the risk for Parkinson’s. It is a joint venture between patients, families and researchers.”
Because of the pioneering Parkinson’s research that is being done in Israel, says Orr-Urtreger, “We have succeeded in putting Israel on the map. Today, when new medicines are being developed for Parkinson’s, drug testing is started in the United States, England and Israel at the same time. The fact that Israelis with the disease are considered equivalent to those in the rest of the world is one of our greatest successes.” Orr-Urtreger adds that while genetic mutations seem to be a cause of Parkinson’s, there are certain genetic changes that can protect against Parkinson’s as well.

ACCORDING TO the Michael J. Fox Foundation for Parkinson’s research, recent studies have shown that the number of cases of Parkinson’s disease is increasing. By 2030, it is estimated that more than a million Americans will have developed the disease. The foundation, which is the world’s largest nonprofit funder of Parkinson’s research worldwide, has supported the research at Tel Aviv for the past 10 years in developing the extensive cohort of patients. In addition, Biogen, one of the world’s leading biotechnology companies, is collaborating with Tel Aviv’s Sourasky Medical Center to develop a treatment that will stop the progression of Parkinson’s disease, and will prevent its occurrence in subjects at risk. Giladi says, “The ultimate goal is that we will know to identify people who are at risk, to figure out when they will become sick and to treat them before they become ill.”
Giladi and Orr-Urtreger are optimistic that a cure for preventing Parkinson’s will be found in the near future.

“I believe that within five to 10 years, we will have significant treatments to prevent the illness,” says Giladi. “This is our dream,” adds Orr-Urtreger. “We think it is possible.”

Some 200 years after Dr. James Parkinson published the first detailed description of the dreaded illness that bears his name, Israeli researchers, in collaboration with scientists around the world are inching ever closer to a cure, providing hope to millions.

This article was written in cooperation with Sourasky Medical Center.
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