132
chapter
8
Enzymes III: Clinical Applications
(e.g., cystic fibrosis),administration of fibrinolytic en-
zymes (e.g., streptokinase) to recanalize blood vessels
occluded by blood clots (thrombi) in thromboembolic
disorders (e.g., pulmonary embolism, acute myocardial
infarction), treatment of selected disorders of inborn er-
rors of metabolism (e.g.,
Gaucher’s disease
), and cancer
therapy
(e.g.,
L-asparaginase
in
acute
lymphocytic
leukemia). For enzymes to be therapeutically useful, they
should be derived from human sources to prevent im-
munological problems. Although enzymes derived from
human blood are readily obtainable, enzymes derived
from tissues, which would be particularly useful in the
treatment of inborn errors of metabolism, are difficult to
obtain in adequate quantities. Transport of specific en-
zymes to target tissues is also a problem, but some recent
advances and commercial applications (e.g., propagation
of human tissue culture cell lines, isolation and cloning
of specific genes) have the potential of overcoming
these difficulties. Such techniques have been used in the
production of peptide hormones such as somatostatin and
insulin, interferon, and tissue plasminogen activator. In the
treatment with enzymes or proteins, covalent attachment
of an inert polymer polyethylene glycol (PEG) provides
many therapeutic benefits. These include slowing the
clearance,
diminished
immunogeneity,
prevention
of
degradation, and binding to antibody. PEG-enzyme ther-
apy is used in the treatment of immunodeficiency disease
caused by adenosine deaminase deficiency (Chapter 27)
and PEG-interferon alfa complex (peginterferon alfa-2a)
is used in treatment of chronic hepatitis C infection.
Ultimately, however, when a gene is cloned, techniques
will be developed to incorporate it into the genome of
persons lacking the gene or having a mutated gene.
Supplemental Readings and References
N. V. Bhagavan, A. P. Goldstein, S. A. A. Honda, et al.: Role of cardiac
troponin I in the evaluation of myocardial injury.
J o u rn a l o f C linical
L a b o ra to ry A n a ly sis
12,
276 (1998).
L. Coudrey: The troponins.
A rch ives o f In te rn a l M ed icin e
158,
1173 (1998).
R. F. Dudley: Chemiluminescence immunoassay: An alternative to RIA.
L a b o ra to ry M ed ic in e
21,
216 (1990).
A. H. Gershlick and R. S. More: Treatment of myocardial infarction.
B ritish
M ed ica l J o u rn a l
316,
280 (1998).
E. A. Kemppainen, J. I. Hedotrom, P. A. Puolakkainen, et al.: Rapid Measure-
ment of Urinary Trypsinogen-2 as a screening test for acute pancreatitis.
N ew E n g la n d J o u rn a l o f M ed icin e
336, 1788 (1997).
K. Mergener and J. Baillie: Acute Pancreatitis.
B ritish M ed ic a l Jo u rn a l
316,
44(1998).
D. S. Pratt and M. M. Kaplan: Evaluation of abnormal liver-enzyme results
in asymptomatic patients.
N ew E n g la n d Jo u rn a l o f M e d icin e
342, 1266
(
2000
).
J. J. Reichling and M. M. Kaplan: Clinical use of serum enzymes in liver
disease.
D ig estive D isea ses a n d S c ien ces
33, 1601 (1988).
W. Steinberg and S. Tenner: Acute pancreatitis.
N ew E n g la n d Jo u rn a l o f
M ed icin e
330, 1198 (1994).
S. Zeuzem, S. V. Feinman, J. Rasenack, et al: Peginterferon alfa-2a in patients
with chronic hepatitis C.
N ew E n g la n d J o u rn a l o f M ed icin e
343, 1666
(2000).
