Cellular prion protein (PrPc) is a high affinity receptor for soluble oligomeric AB42 (see Figure 2, Strittmater
et al., 2010), mediating toxic effects on synaptic plasticity. PrPc represents a target in Alzheimer?s disease
(AD) directly disrupting the signaling pathway of soluble A?42.
address the following questions.
1) Describe an in vivo experiment that would validate this target as a disease modifying therapy for AD using a
specific monoclonal anti-PrPc antibody. In your answer justify and describe your chosen disease animal model of
AD, treatment groups and chosen endpoints to measure disease modification. Discuss the validity of your chosen
disease animal model.
2) Define the term pharmacodynamic (PD) marker. Describe why PD markers are essential to any drug development
programme. Propose a possible PD marker for an anti-PrPc antibody.
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