Figure 2. The mouse and human brains have clear morphological Figure 3. A closer look at the difference between human and mouse brains
differences (images not to scale).
(images not to scale).
Source: Elizabeth Atkison, Washington University in St. L
When developing a new drug, phar-
maceutical companies run several
animal tests to ensure both efficacy
and safety before proceeding to hu-
man trials. Simply put, it is not com-
mon to test a drug in humans without
it first entering the mouse. From this
point of view, the mouse is clearly in-
tegral to drug development. However,
it is important to realize that animal
models do not always reliably predict
the outcome in humans as tragically
demonstrated in a recent Phase I hu-
man clinical trial conducted in France.
Six people were hospitalized and one
participant died from neuronal compli-
cations resulting from a new pain and
anxiety medication even after rats,
mice, dogs, and monkeys were pre-
viously treated with the medication
without problems (though there were
allegations that dogs suffered unre-
ported side effects) [1].
Needless to say, working with bio-
logically active compounds is danger-
ous business, but this work needs to
be done if we as a society are to im-
prove upon the current standard of
treatment. On the other hand, mouse
models of breast cancer have pro-
duced results of varying relevance
for humans, [2] but despite missteps
along the way, this work has resulted
in improvements in human treatment.
Mouse models of BRCA mutations (a
breast cancer associated gene) have
shed new light on mechanistic insights
and potential treatments for patients.
For example, there are currently inhib-
itors of DNA repair mechanisms (PARP
inhibitors) in Phase III clinical trials for
the treatment of breast cancer (see
Talazoparib and Veliparib). Researchers
believe that by inhibiting the DNA re-
pair pathway, cancers cells die faster
Source: Cryan JF, Holmeands A. Nat Rev Drug Discov. 2005. Sep;4:775-90
because these cells tend to divide
faster than their healthy counterparts.
Research into another breast cancer
associated protein known as HER-
2 has resulted in the production and
approval of the monoclonal antibody
Trastuzumab (an antibody is a mole-
cule that binds to a protein). Scientists
discovered that HER-2 is elevated in
a subset of breast cancer patients’
tumors and then subsequently used
laboratory mice to develop the first
antibodies against the HER-2 protein
[3]. This medication transformed a
devastating diagnosis into one that is
not without hope and is listed on the
World Health Organization’s (WHO)
model list of essential medicines.
These types of medicines demon-
strate that mouse models of human
disease are not without value. Pain
research is another area that has
gained new insight with the help of
mice. Clearly different individuals have
diverse pain tolerances. We all know
that coworker who shrieks in agony
from a paper cut and the contrasting
stoic who hardly flinches after drop-
ping an 80 kg machine on their foot.
Relatedly in mice, there is interest-
ing research led by Prof. Jeff Mogil of
McGill University on the variability in
pain tolerance across mouse strains
[4]. Simply stated, on one end of the
spectrum there are mouse strains
with a high pain tolerance whose tol-
erance is further strengthened by an-
algesics, while on the other end exist
mouse strains with a low pain toler-
Figure 4. Pain sensitivity varies across mouse strains at an order of 1.2 to 54-fold.
Source: Mogil JS et. al. Pain. 1999;80:67-82
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