Uses for Recombinant Protein Drugs - Biotechnology and Your Health: Pharmaceutical Applications - page 63

called macrophages fill up with cerebroside, and large numbers of
these fat-loaded cells settle in the liver, bone marrow, and spleen
(the large blood-forming organ located above the liver). In
Gaucher disease, patients' bones may not develop normally and
may break without trauma, because macrophage-related cells are
involved in bone formation and destruction. The Gaucher cells
may also cause severe pain, because macrophages carry proteins
that cause pain, which they can emit where they accumulate. The
new treatment for this inherited disease is an example of a
modern biotechnology drug replacing a conventionally derived
drug, much like insulin and growth hormone. In 1991, researchers
produced large amounts of the normal form of the enzyme from
human placentas (the organ that delivers nutrients to the fetus
while it is inside the womb) but the enzyme as isolated did not
work as a treatment because the accumulated cerebroside is inside
the Gaucher cells and the isolated enzyme could not enter the
cells. To solve this problem, scientists attached sugar molecules to
one end of the enzyme protein—not just any sugars but those that
would specifically trigger the Gaucher cells to suck in the enzyme.
The scientists knew which sugars instructed macrophages to con-
sume things. The particular sugar they attached fit neatly into a
receptor on the surface membrane of the macrophage/Gaucher
cells and when the sugar-linked enzyme landed on the receptor,
the cell membrane folded into a little balloon and engulfed the
sugar/protein package.
The placenta-derived enzyme was treated to make any associ-
ated risk of viral infections low, but a small risk of infection from
human tissue remained, so scientists developed a recombinant
replacement enzyme, with the right sugar embellishment, produced
from a laboratory source. Unfortunately, about 15% of patients
treated with the replacement enzyme develop antibodies to the
protein that can reduce the usefulness of the injections and pose a
risk of mild to severe allergic reactions. At the moment, however,