Limitation of animal models in drug discovery and development

1
Limitation of animal models in drug discovery and
development

• ? Animal cells may not always simulate complex
  biochemical mechanisms of human disease
• Is the observed disease phenotype in the animal
  equivalent to that of the human counterpart?

Hence, there is a need to use human cells to test
the efficacy of candidate drugs.
Candice Tahimic, Ph.D.
2
Human ES or iPS cells can be converted into
dopaminergic neurons for use as cell models of
Parkinsons disease
Midbrain dopaminergic neurons in the substantia
nigra are selectively lost in Parkinsons disease
Certain psychiatric disorders and certain
addictions (nicotine and cocaine dependence) are
thought to be mediated by the dopaminergic system
Candice Tahimic, Ph.D.
3
Human cell models for disease the promise of
hES/iPS cells
Human ES cell
The iPS or hESC -derived neurons are treated with
a number of candidate drugs for a particular
disease. The neurons are then observed for
reversal of the disease phenotype. Promising test
compounds are further validated.
Dirrected differentiation
F
B
Chemical library screening
C
On-dish assay for efficacy
A
Reporter levels
D
E
Test compound
Neurons
Candice Tahimic, Ph.D.