Biomedical Engineering Reference
In-Depth Information
can be recognized in otherwise healthy animals. There are
a number of well-described disease models in the
nonhuman primate available in various specialty laborato-
ries (
Thomas et al., 1999, Kavanagh et al., 2011
). These
colonies can provide unique test subjects with disease states
that are very relevant to human patients; however, these
studies often have increased inter-test subject variability as
these animals are often older and may have other concur-
rent health issues that can confound data interpretation.
Utilizing physiological manipulation in younger healthy
animals can sometimes demonstrate test compound effi-
cacy more directly. For example, for a compound designed
to manage glucose metabolism, studies can be run in aged
nonhuman primates that have developed spontaneous Type
II diabetes, or glucose tolerance tests can be done in
younger healthy animals (
Glaesner et al., 2010
). Both
strategies have unique advantages and disadvantages that
need to be considered for each program.
Baille, T. A., Cayen, M. N., Fouda, H., Gerson, R. J., Green, J. D.,
Grossman, S. J., et al. (2002). Contemporary issues in toxicology,
drug metabolites in safety testing. Toxicol. Appl. Pharmacol., 182,
188
196.
Baldrick, P. (2010). Safety evaluation of biological drugs: what are
toxicology studies in primates telling us? Regul. Toxicol. Pharmacol.,
59, 227
e
236.
Baumann, A. (2009). Foundation review: nonclinical development of
biopharmaceuticals. Drug Discovery Today, 14, 1112
e
1122.
Bellino, F. L., & Wise, P. M. (2003). Nonhuman primate models of
menopause workshop. Biol. Reprod., 68,10
e
18.
Blackwood, R. S., Tarara, R. P., Christe, K. L., Spinner, A., &
Lerche, N. W. (2008). Effects of the macrolide drug tylosin on
chronic diarrhea in rhesus macaques (Macaca mulatta). Comp. Med.,
58,81
e
87.
Brennan, F. R., Morton, L. D., Spindeldreher, S., Kiessling, A.,
Allenspach, R., Hey, A., et al. (2010). Safety and immunotoxicology
assessment of immunomodulating monoclonal antibodies. MAbs
(Epub)., 2, 233
e
255.
Burton, N. C., & Guilarte, T. R. (2009). Manganese neurotoxicity: lessons
learned from longitudinal studies in nonhuman primates. Environ-
ment. Health Perspect., 117, 325
e
332.
Buse, E., Cline, J. M., de Rijk, E. P. C. T., van Esch, E., Vidal, J. D.,
Weinbauer, G. F., et al. (2008). A monograph on female reproductive
pathophysiology in macaques. Toxicol. Pathol., 36,5S
e
Conclusions
Efficacy studies in nonhuman primates have the potential to
yield rewarding data, but they are complicated technically
and sometimes ethically. Positive control groups, which are
a standard in rodent efficacy work, can raise more questions
during ethical reviews than with the lower order species.
Proper management of these studies requires that the
biologist engage veterinarians, model specialists, patholo-
gists, and technical experts to design and interpret these
often complicated studies.
7S.
Cavagnaro, J. A. (2008). The principles of ICH S6 and the case-by-case
approach. In J. A. Cavagnaro (Ed.), Preclinical Safety Evaluation of
Biopharmaceuticals: a science based approach to facilitating clinical
trials (pp. 45
e
66). Hoboken: John Wiley & Sons.
Cefalu, W. T. (2006). Animal models of type 2 diabetes: clinical
presentation and pathophysiological relevance to the human condi-
tion. ILAR J., 47, 186
e
198.
Chapman, K., Pullen, N., Coney, L., Dempster, M., Andrews, L.,
Bajramovic, J., et al. (2009). Preclinical development of monoclonal
antibodies: considerations for the use of non-human primates. mAbs.,
1, 505
e
516.
Chapman, K. L., Pullen, N., Andrews, L., & Ragan, I. (2010). The future
of non-human primate use in mAB development. Drug Discovery
Today, 15, 235
e
242.
Chellman, G. R., Bussiere, J. L., Makori, N., Martin, P. L., Ooshima, Y.,
& Weinbauer, G. F. (2009). Developmental and reproductive toxi-
cology studies in nonhuman primates. Birth Def. Res. Part B, 83,
1
e
17.
Chyan, Y. J., &Chuang, L. M. (2007). Dipeptidyl peptidase-iv inhibitors: an
evolving treatment for type 2 diabetes from the incretin concept. Recent
Patents Endocrine, Metab. Immune Drug Discovery, 1,15
e
24.
Code of Federal Regulations (CFR) (1999). Food and Drugs, Chap. 21.
Cosenza, M. E. (2008). Implementation of ICH S6: US perspective. In
J. A. Cavagnaro (Ed.), Preclinical Safety Evaluation of Bio-
pharmaceuticals: a science based approach to facilitating clinical
trials (pp. 111
e
REFERENCES
Abbott, D. H., Barnett, D. K., Colman, R. J., Yamamoto, M. E., &
Schultz-Darken, N. J. (2003). Aspects of common marmoset basic
biology and life history important for biomedical research. Comp.
Med., 53, 339
e
350.
Adolphs, R. (1999). Social cognition and the human brain. Trends
Cognitive Sci., 3, 469
479.
Aleo, M. D., Lundeen, G., Blackwell, D. K., Smith, W. M.,
Coleman, G. I., Stadnicki, S. W., et al. (2003). Mechanism and
implications of brown adipose tissue proliferation in rats and
monkeys treated with the thiazoldinedione darglitazone, a potent
peroxisomes proliferator-activated receptor-
g
agonist. J. Pharm. Exp.
Ther., 305, 1173
e
1182.
Anderson, T. D., Hays, T. J., Powers, G. D., Gagtely, M. K., Tudor, R., &
Rushton, A. (1993). Comparative toxicity and pathology associated
with administration of recombinant IL-2 to animals. Int. Rev. Exp.
Pathol., 34A,57
e
77.
Attarwala, H. (2010). TGN1412: from discovery to disaster. J. Young.
Pharm., 2, 332
e
336.
Bagi, C. M., Wood, J., Wilkie, D., & Dixon, B. (2008). Effect of 17beta-
hydroxysteroid dehydrogenase type 2 inhibitor on bone strength in
ovariectomized cynomolgus monkeys. J. Musculoskelet. Neuronal.
Interact., 8, 276
e
280.
e
122). Hoboken: John Wiley & Sons.
Czoty, P. W., Gould, R. W., & Nader, M. A. (2009). Relationship between
social rank and cortisol and testosterone concentrations in male
cynomolgus monkeys (Macaca fascicularis). J. Neuroendocrinol., 21,
68
e
76.
Dempster, A. M. (2000). Nonclinical safety evaluation of bio-
technologically derived pharmaceuticals. Biotechnol. Annu. Rev.,
5,221
e
258.
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