"As the first effective drug treatment for Gaucher's disease, this therapy offers patients who have been saddled with chronic and debilitating symptoms the chance to break free from disease," said Dr. Norman Barton, M.D., Ph.D., the NINDS scientist who directed the study. "Patients treated in the study not only experienced a dramatic reduction in objective disease signs, they also reported impressive gains in energy, self-confidence and quality of life."

In Type I Gaucher's disease, the body lacks sufficient levels of an enzyme called glucocerebrosidase needed for breakdown of a fatty material, or lipid. The deficiency causes lipid to accumulate, swelling the spleen and liver, crowding out the marrow in the bones, and triggering anemia and low blood platelet counts. These patients often suffer from fatigue, grossly distended abdomens, joint and bone pain, repeated bone fractures, and increased bruising and bleeding. Enzyme replacement therapy replenishes the lacking glucocerebrosidase with a modified version of the enzyme, known generically as alglucerase and sold under the trade name Ceredase.

In the recent study, 12 patients with symptomatic Type I Gaucher's disease were treated every two weeks with intravenous infusions of the drug for periods ranging from 9-12 months. Therapy increased levels of hemoglobin in all patients. It also boosted platelet counts in seven patients, produced bone improvement in three patients, reduced liver size in five patients, and decreased spleen enlargement among all patients by an average of one-third. No adverse effects were observed. "Enzyme replacement is remarkably safe, and it appears to benefit all patients with Type I Gaucher's disease," Dr. Barton said.

In addition, all of the treated patients reported increased energy, improved self-esteem and self-image, and greater ease and self-confidence in daily activities.

While patients in this study received high doses of enzyme, NINDS scientists are now working to determine the lowest dose needed to reverse symptoms. They have also begun studies to define how much enzyme patients need in order to stay healthy once their blood counts have recovered to normal, since lipid buildup would resume in patients without continued therapy.

Most traditional treatments for Gaucher's disease, such as removal of an enlarged spleen, relieve some symptoms but do not slow disease progression. Although bone marrow transplantation can sometimes reverse the disease, it is a relatively risky procedure.

Ceredase is derived from human tissues, purified, then chemically altered in order to target the cells with lipid buildup. This technique for altering the natural enzyme could suggest treatments for other metabolic diseases, said NINDS scientist Roscoe Brady, M.D., who pioneered enzyme replacement therapy for Gaucher's disease through more than 30 years of research.

"The targeting strategy we've developed to deliver enzyme in this disorder is a prototype," said Dr. Brady, chief of the NINDS Developmental and Metabolic Neurology Branch. "It can be applied to an entire class of inherited diseases where the body lacks vital proteins, including other lipid storage disorders. We plan to investigate this possibility," he said.

Gaucher's disease has three forms and affects all racial and ethnic groups. Type I is the most common genetic disorder among people of Eastern European Jewish descent -- as many as one in 10 of this group is estimated to carry one copy of the defective gene. In the rarer and more severe Types II and III, the abnormal lipid storage also affects the nervous system. NINDS scientists are working to determine the effects of enzyme replacement therapy in Gaucher's patients with neurological complications.

Ceredase is manufactured by the Genzyme Corporation of Cambridge, Massachusetts, and was approved by the FDA in early April for treatment of Type I Gaucher's disease.

The National Institute of Neurological Disorders and Stroke, one of the 13 National Institutes of Health in Bethesda, Maryland, is the primary supporter of brain and nervous system research in the United States.

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*Barton NW, Brady RO, Dambrosia JM., et. al. Replacement therapy for enzyme deficiency: Macrophage-targeted Glucocerebrosidase for Gaucher's Disease. The New England Journal of Medicine, May 23, 1991.