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Disease Influence on BBB Transport in Neurodegeneration

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Drug Delivery to the Brain

Part of the book series: AAPS Advances in the Pharmaceutical Sciences Series ((AAPS,volume 33))

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Abstract

For the pharmacotherapy of neurodegenerative diseases, drugs must pass the blood–brain barrier (BBB). The BBB seems to play an important role in disease initiation and or progression, and many changes in BBB properties in neurodegeneration have been reported. In vivo studies including measurements of unbound drug concentrations in plasma and brain are needed for insight into BBB transport, intra-brain and target site distribution, and specific changes related to neurodegenerative conditions. However, it is surprising that only a limited number of such studies have been performed to date. This chapter summarizes the published work on these in vivo studies and provides a perspective on what is needed to advance and foster more understanding in the future . Though it is generally thought that the BBB is compromised in neurodegenerative disorders, quantitative studies indicate that this is not necessarily always the case. It is recommended to increase in vivo studies that can integrate the impact of neurodegenerative processes, to complement studies on neurodegenerative components in isolation, and to improve our understanding of target site distribution of drugs intended to treat the disease condition. As in vivo studies on human brain sampling are ethically restricted, we must rely on animal models and translational mathematical approaches to infer relevance for clinical work.

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Authors and Affiliations

  1. Research Division of Systems Pharmacology and Pharmacy, Leiden University, Leiden, The Netherlands

    Elizabeth C. M. de Lange

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  1. Elizabeth C. M. de Lange
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Correspondence to Elizabeth C. M. de Lange .

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Editors and Affiliations

  1. Research Division of Systems Pharmacology and Pharmacy, Leiden University, Leiden, The Netherlands

    Elizabeth C.M. de Lange

  2. Department of Pharmacy, Uppsala University, Uppsala, Sweden

    Margareta Hammarlund-Udenaes

  3. Biology Discovery, Denali Therapeutics, South San Francisco, CA, USA

    Robert G. Thorne

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de Lange, E.C.M. (2022). Disease Influence on BBB Transport in Neurodegeneration. In: de Lange, E.C., Hammarlund-Udenaes, M., Thorne, R.G. (eds) Drug Delivery to the Brain. AAPS Advances in the Pharmaceutical Sciences Series, vol 33. Springer, Cham. https://doi.org/10.1007/978-3-030-88773-5_22

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