Roscoe O. Brady
National Institute of Neurological Disorders and Stroke, NIH
Elizabeth F. Neufeld
National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases, NIH
For pioneering contributions to the understanding of hereditary diseases, the development of effective genetic counseling procedures, and initiation of possible treatment by replacement of missing enzymes.
Because of a metabolic defect, the body tissues of persons afflicted with these disorders begin to accumulate and store an excessive amount of fatty materials called lipids. The accumulating lipids may cause enlargements of the spleen and liver, damage to the bones and kidneys, failure of major organs, and often early death.
In a series of elegant experiments, Dr. Brady discovered the precise metabolic defect—a particular missing enzyme—which causes the lipids to build up and destroy body tissues. In demonstrating this to be the case for such disorders as found in Gaucher disease, Niemann-Pick disease, Fabry disease, and Tay-Sachs disease, Dr. Brady solved an enigma that had confounded medical practitioners for nearly a century.
Dr. Brady’s discoveries now provide the basis for the early diagnosis of the diseases, for the identification of those who might pass on the disorders to their children, and for the detection of the diseases prenatally.
The present and continuing thrust of Dr. Brady’s investigations deal with the treatment of the disorders. In his efforts to find a promising treatment, Dr. Brady is attempting to learn how to replace the missing enzyme, thus reducing the buildup of destructive lipids and preventing the damage they cause.
To Dr. Brady, for his outstanding accomplishments in the diagnosis and potential treatment of the lipid storage diseases, this 1982 Albert Lasker Clinical Medical Research Award is given.
For clarifying the molecular basis and diagnosis of certain hereditary lysosomal storage disorders that may cause growth abnormalities, blindness, deafness and death.
In these genetic diseases, the best known of which are Hunter and Hurler syndromes, excessively high quantities of mucopolysaccharides—cell products composed of complex sugars—accumulate in the body tissues, leading to skeletal abnormalities, intellectual disabilities, blindness and deafness. The diseases are often fatal.
Using creative and intricate research methods over the past 15 years, Dr. Neufeld demonstrated that these disorders stem from defects in degradative enzymes. She also demonstrated that the excess mucopolysaccharides accumulated within lysosomes—the minute cellular organs in which large molecules are broken down—thus also defining these conditions as lysosomal storage disorders. Additionally she discovered the specific enzyme deficiencies involved in several diseases of this group.
The work of Dr. Neufeld represents the major foundation upon which our understanding of these genetic disorders is now based. She also developed the special methods and chemicals that now make it relatively easy to diagnose patients with these diseases and to perform prenatal diagnosis of these diseases. This work has also led to new concepts regarding the transport of enzymes to lysosomes, with implications for basic cell biology and for possible enzyme replacement.
To Dr. Elizabeth Neufeld, whose pioneering work has uniquely contributed to our basic knowledge of an important group of hereditary diseases, this 1982 Albert Lasker Clinical Medical Research Award is given.