Therapy for inherited enzyme deficiencies

1991

Challenge

Gaucher disease stems from deficiency of the enzyme glucocerebrosidase, leading to accumulated lipids that cause symptoms ranging from mild pigmentation to life-threatening seizures and brain damage. Although the concept of enzyme replacement had been proposed many years ago, a targeted approach is needed to ensure delivery of the enzyme to the correct cell type.

Advance

IRP researchers led by Roscoe Brady, M.D., developed a macrophage-targeted glucocerebrosidase, designed to deliver the missing enzyme directly into the macrophages of patients with Gaucher disease. The team conducted the first clinical trial with the new therapy and observed a reversal of all symptoms in all patients.

Impact

Doctors have now established intravenous administration of macrophage-targeted glucocerebrosidase as an effective treatment for the symptoms of Type 1 and Type 3 Gaucher disease NINDS Gaucher Disease Information Page. For his research, Dr. Brady was awarded the National Medal of Technology and Innovation in 2008, the highest honor for achievement in science and technology bestowed by the U.S. President Dr. Roscoe Brady Receives Presidential Honor for Scientific Achievement.

Publications

Barton NW, Brady RO, Dambrosia JM, Di Bisceglie AM, Doppelt SH, Hill SC, Mankin HJ, Murray GJ, Parker RI, Argoff CE, et al. (1991). Replacement therapy for inherited enzyme deficiency--macrophage-targeted glucocerebrosidase for Gaucher’s disease. N Engl J Med. 324(21), 1464-70.