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Making AD mice as diverse as patients

How adding genetic diversity to Alzheimer’s mice could help define responders

The Jackson Laboratory aims to make Alzheimer’s disease mouse models more useful for predicting which patients will respond to therapy by engineering in a high degree of genetic diversity to better reflect trial populations.

The numerous AD therapies that have failed in the clinic after producing convincing data in mice underscores the need for more predictive animal models. Even Biogen Inc.’s promising Phase Ib data from aducanumab, slated for a Phase III readout early next year, suggest the anti-amyloid mAb will likely only benefit a subset of patients. Last February, after observing variability in the Phase III data, Biogen increased Phase III enrollment to ensure the studies would be powered to see an effect on the primary endpoint.

One goal of better mouse models is to refine the patient population from the outset.

In a Neuron study published last week, the JAX group departed from a central tenet of mouse modeling to create a population that mimics more closely the genetic and behavioral diversity seen in AD patients.

Normally, genetic mouse models are made by introducing disease-linked mutations into standard laboratory mouse lines, which are identical at all other alleles across the genome. This is done to simplify data interpretation by making sure

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