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Leap ahead in treatment for Jews' genetic disease

By Charlotte Halle

Ha'aretz, September 8, 2000


Doctors are hoping a major breakthrough will be announced today at a conference in Jerusalem on the treatment of Gaucher disease. The rare genetic disorder is most commonly found among Ashkenazi Jews. (See box)

One hundred and seventy doctors, scientists and representatives of patients' groups at the Fourth Meeting of the European Working Group on Gaucher disease will hear the latest results on trials into OGT-918, a newly developed oral medicine to treat the genetic disease.

"We are hoping there will be a breakthough in treatment," says Dr. Ari Zimran, director of the Gaucher Clinic at Shaare Zedek Hospital, the world's largest center in treating patients with the rare genetic disease.

"Until today, there has been a monopoly with only one company working on Gaucher disease. Now there is more competition and it will be better for patients," Zimran said. 'Whole new concept' He added that developments could lead to a "whole new concept" in treating all lysosomal storage disorders - which include Tay-Sachs disease and Niemann-Pick disease - also more prevalent among Ashkenazi Jews than any other ethnic group.

The British company Oxford GlycoSciences, manufacturers of OGT-918, published the first round of findings from clinical trials in April of this year. Results of the trials, which were conducted in Cambridge, Prague, Amsterdam and Jerusalem, indicate that the orally administered drug is a contender to replace the current leading treatment for Gaucher disease patients - enzyme replacement therapy.

The last major breakthrough in treating Gaucher disease came 10 years ago when enzyme replacement therapy hit the market. The first effective treatment for Gaucher disease, it works to stop its progression and can even reverse symptoms.

The cost of the treatment, however, is prohibitive for many patients: It costs $100,000 per year in Israel to treat an average adult weighing 70 kilograms.

In the United States, where a higher dose is administered, costs can reach $400,000 a year per patient. Doctors hope the new drug will be significantly less expensive. They also hope it will help more people - the treatment is not administered intravenously as with enzyme replacement therapy - a method which has detered some patients.

U.S.-born Dr. Deborah Elstein, also of the Gaucher Clinic at Shaare Zedek Hospital, says that having seen results of trials on the new drug, it seems "comparable with enzyme replacement therapy," yet without some of its drawbacks.

A number of doctors and researchers involved in the trials around the world, including Zimran who administered OGT-918 to Gaucher patients in Jerusalem, will present their findings at the final session of the conference this afternoon. If the findings revealed continue to compare to those of enzyme replacement therapy, it will take the drug a step closer to receiving the all-important U.S. Food and Drug Administration (FDA) approval.

Other sessions at the conference, which began on Wednesday, have focused on bone marrow transplantation for the correction of genetic diseases, patient societies and Fabry disease. It is the first time American experts in the field of Gaucher disease will be participating in the European conference forum. An incurable but treatable disorder

People with Gaucher disease lack an important enzyme that the body needs to break down a particular kind of fat. This leads to the storage of fat in the liver, spleen and bone marrow, causing them to lose their normal functions.

Symptoms range from mild to severe and many patients suffer from anemia, bone damage and enlarged livers and spleens. The inherited disorder is incurable, but can be treated by blood transfusions, removal of the spleen, painkillers, surgery to correct bone problems and bone marrow transplants, as well as enzyme replacement therapy.

Gaucher disease is the most common genetic disorder among Jews; an estimated one in 10 Ashkenazi Jews is a carrier for Gaucher disease. Gaucher specialist, professor Ari Zimran says that one in a thousand Ashkenazi Jews has the disease, but only one in five of these is symptomatic.

There are three types of Gaucher disease. While Type I is more prevalent among Ashkenazi Jews this is not the case with Types II and III, which affect the central nervous system and can not be treated by enzyme replacement therapy.

Doctors at the Gaucher Clinic at Shaare Zedek Hospital have detected a unique variant of Gaucher disease, in which the heart is the most affected organ; most patients identified so far are Arabs from the area of Jenin.

Screening for carriers, though widely available in Israel, is controversial. Many doctors, including Zimran, believe that as most patients with Gaucher disease are asymptomatic, screening is unnecessary.

"In our philosophy, screening should be done for diseases which are fatal or with severe morbidity. There is no need to do large scale screening for a mild, benign disease, which is treatable," says Zimran. "We see a very bright future for people with Gaucher disease.




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