What question did this study set out to answer?

To determine whether coupling the amyloid-degrading enzyme neprilysin to a Brain Shuttle module enables transport across the blood-brain barrier to reduce central amyloid-β levels.

March 10, 2020PLoS ONEOpen Access

Brain Shuttle Neprilysin reduces central Amyloid-β levels

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To determine whether coupling the amyloid-degrading enzyme neprilysin to a Brain Shuttle module enables transport across the blood-brain barrier to reduce central amyloid-β levels.
Engineered fusion proteins linking the extracellular catalytic domain of neprilysin to an active or inactive transferrin receptor-targeting Brain Shuttle module.
Assessed pharmacokinetic and pharmacodynamic relationships across blood and cerebrospinal fluid compartments using single-dose response and multiple-dosing regimens.
Systemic administration of unmodified neprilysin effectively cleared amyloid-β in peripheral blood but achieved no reduction in the cerebrospinal fluid compartment.
Active Brain Shuttle neprilysin achieved substantial cerebrospinal fluid exposure and drove significant amyloid-β reduction in both cerebrospinal fluid and brain parenchyma.

Authors

CCChristopher CamposUniversity of California, Davis AKAlicia M. KembleRoche (Switzerland)JNJens NiewoehnerRoche (Switzerland)

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Implication

Preclinical study demonstrates reduced central amyloid-β in animal models, suggesting effective blood-brain barrier enzyme delivery for Alzheimer's disease therapeutics.

Cite This Study

Campos et al. (2020) studied this question.

synapsesocial.com/papers/6a7d7fd8a4ba4076882080e9 https://doi.org/10.1371/journal.pone.0229850

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Implication

Preclinical study demonstrates reduced central amyloid-β in animal models, suggesting effective blood-brain barrier enzyme delivery for Alzheimer's disease therapeutics.

Brain Shuttle Neprilysin reduces central Amyloid-β levels

Key Points

Discussion

Implication

Cite This Study

Brain Shuttle Neprilysin reduces central Amyloid-β levels

Key Points

Discussion

Implication

Cite This Study

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