Altered enzyme reverses Gaucher's symptoms.

Roscoe O. Brady first proposed enzyme-replacement therapy for Gaucher's disease 25 years ago. A tantalizing series of experimental ups and downs followed, but never quite produced the hoped-for cure. Now, Brady and his colleagues outline a new twist on the enzyme treatment, one that provides dramatic relief from the major symptoms of this debilitating and sometimes lethal disease.

People with Gaucher's disease inherit a defective enzyme that cannot break down a fatty substance called glucocerebroside. As a result, the fatty material builds up in scavenger cells of the immune systems, called macrophages. The fat-engorged macrophages cluster in the liver and spleen, causing these organs to swell. Symptoms of the disease, which strikes about one in 40,000 people in the United States, include bone loss, excruciating bone pain, internal bleeding, and severe anemia involving a decrease in the oxygen-carrying hemoglobin within red blood cells.

Previous attempts to treat Gaucher's disease with injections of the fully functioning enzyme failed because scientists couldn't get enough of the lifesaving substance into the patients' macrophages. In the May 23 NEW ENGLAND JOURNAL OF MEDICINE, Brady and his colleagues report that a modified enzyme therapy produced striking improvement in 12 adults and children with moderate to severe Gaucher's. The team used chemically treated enzyme that binds and enters macrophages.

Patients received intravenous injections of the modified enzyme once every two weeks in moderate cases and once a week in severe cases. After six months of treatment, five participants showed a 16 to 22 percent reduction in liver size and all 12 showed a significant reduction (averaging 33 percent) in spleen size. The most dramatic finding, however, was an increase in all patient's hemoglobin, which reached normal levels in seven individuals. Three people also showed signs of increased bone density, and Brady thinks others may follow suit after several more years of treatment.

All volunteers reported less fatigue and most experienced less pain, the researchers note. In two particularly severe cases, children who had been virtually crippled by the disease resumed normal activities, says Brady, of the National Institute of Neurological Disorders and Stroke in Bethesda, Md.

The new treatment "completely reverses the pathology of the disease," he told SCIENCE NEWS.