Unit Director: Prof. Ari Zimran

Tel: 02.655.5760    02.655.5330

Location: 5th floor

Areas of Activity:

The Gaucher Clinic was established in October, 1989 as the first national referral out-patient clinic for patients with Gaucher disease by Prof. Ari Zimran. Being the most common inherited disorder affecting Ashkenazi Jews, Gaucher disease is especially prevalent in Israel. While it is obvious that the frequency of the disease in this population is higher than initially estimated, it is still a rather rare disease, and many patients are often treated by physicians of various disciplines who were not familiar with all the nuances of Gaucher disease manifestations. More importantly, general practitioners are not always aware of the new treatment modalities and adjuvant therapies.
 

Patients with Gaucher disease come to our clinic for complete baseline evaluation, for follow-up examinations, for consultations regarding specific conditions such as army service, pregnancy etc, and for treatment. We have established a team approach with senior specialists in all the relevant fields of medicine, including pediatricians, surgeons, orthopedists, gynecologists, pulmonologist, hematologist, radiologist, and both pediatric and adult neurologists. Some of these specialists see the patients at each visit, while others are available as consultants for different patients and at different times in the course of follow-up. With over 600 patients currently being monitored in our clinic, each of these specialists has also developed considerable expertise in the manifestations of Gaucher disease and hence each is uniquely qualified to deal with Gaucher patients. Our clinic is a separate unit within the Department of Medicine in Shaare Zedek Medical Center and Prof. Zimran is also affiliated with the Hadassah School of Medicine - Hebrew University in Jerusalem.
 
Our clinic was the first medical group outside the US to introduce enzymatic replacement therapy (ERT) with alglucerase (Ceredase®, Genzyme Inc., MA) in December, 1990 and was also active in lobbying for its registration by the Ministry of Health in Israel. Our clinic was involved in the seminal trial of the recombinant form of the enzyme, imiglucerase (Cerezyme®, Genzyme Therapeutics Inc., MA) in 1992 and its registry in 1994. We currently treat about nearly 200 symptomatic patients, both adults and children, with this standard of care and oversee the world largest cohort of Gaucher patients. Enzyme replacement therapy with Cerezyme prevents progressive manifestations of Gaucher disease, and completely or partially ameliorates Gaucher disease-associated anemia, thrombocytopenia, organomegaly, bone pain, and bone crises. This treatment, however, is very expensive.
 
From 1998-2002 our clinic was involved in three pivotal trials using miglustat, testing the safety and efficacy of the concept of substrate reduction therapy (SRT) as a therapeutic regimen. Miglustat, now named Zavesca® (Actelion Therapeutics, Allschwil, Switzerland) has been approved and licensed for treatment of type I Gaucher disease by the European EMEA in November 2002 and by the American FDA in July 2003. However, due to inferior efficacy and problematic safety profile, this drug is currently indicated only to those patients for whom enzyme therapy in unsuitable or not a therapeutic option) according to EMEA and FDA, respectively.
 
We have also been the single center to conduct a Phase I/II clinical trial with a native sequence enzymatic preparation – gene activated glucocerebrosidase (GA-GCB®) by the Shire Human Genetic Therapies (Cambridge, MA, USA); 24 months have been completed and recruitment of patients for Phase III trials is anticipated shortly. Currently, too, a plant-derived intravenous enzyme preparation by the Protalix Corporation (Carmiel, Israel) is recruiting naןve patients for a Phase III trial, including in our clinic. The Genzyme Corporation (Cambridge, MA, USA) is also enrolling patients from our clinic for a muti-national multi-center clinical trial of a ceramide analog for a new oral substrate reduction therapy.

An emerging interest of our clinic is a resultant of the above multiple clinical options in a rare, non-lethal disease, and hence we are beginning to inquire into the ethical underpinnings of recruitment into clinical trials, conflicts of interest, etc.

Prof Ari Zimran, together with Prof. Anthony Futerman from the Weitzmann Institute, has recently edited a comprehensive new textbook on Gaucher disease. In this book, for the first time, there is (in addition to the basic science and clinical features) a series of chapters, 2 of them written by Dr. Deborah Elstein from the Gaucher Clinic, dealing with ethical, societal and medical considerations associated with Gaucher disease as a model for other lysosomal storage diseases and orphan diseases, in general, making this book very relevant and important beond Gaucher disease.

Our clinic has also taken an active interest in the very rare clinical entity of Late-onset Tay-Sachs disease (LOTS), which also has a predilection among Ashkenazi Jews. We currently are following about 15 patients of the approximately 100 patients identified throughout the world. Our hope is to have some of these patients participate in appropriate clinical trials with therapy that can traverse the blood-brain barrier and thereby impact the trajectory of the neurological decline.

Among our more important publications that are separate from those relating to clinical trials per se are: our successful experience with low-dose, low-frequency enzyme therapy, description of an unique variant of Gaucher disease among Arabs with progressive calcification of the heart valves, the seminal description of an early-onset form of parkinsonism in patients with Gaucher disease, the ethical considerations involved in providing enzyme therapy to babies with the neuronopathic forms of Gaucher disease, outcome of pregnancies in women with Gaucher disease, an echocardiographic study of pulmonary hypertension among patients with Gaucher disease, follow-up of patients who have undergone orthopedic interventions especially hip replacements, the lack of predilection for cancers (other than multiple myeloma) among patients with Gaucher disease, use of anesthesia in pregnant patients with Gaucher disease and in those undergoing orthopedic surgeries, and the impact of expensive therapies on national health budgets.