Targeting Therapeutic Antibodies to the CNS: a Comparative Study of Intrathecal, Intravenous, and Subcutaneous Anti-Nogo A Antibody Treatment after Stroke in Rats


Loading...

Date

2020-07

Publication Type

Journal Article

ETH Bibliography

yes

Citations

Altmetric

Data

Abstract

Antibody-based therapeutics targeting CNS antigens emerge as promising treatments in neurology. However, access to the CNS is limited by the blood–brain barrier. We examined the effects of a neurite growth-enhancing anti-Nogo A antibody therapy following 3 routes of administration—intrathecal (i.t.), intravenous (i.v.), and subcutaneous (s.c.)—after large photothrombotic strokes in adult rats. Intrathecal treatment of full-length IgG anti-Nogo A antibodies enhanced recovery of the grasping function, but intravenous or subcutaneous administration had no detectable effect in spite of large amounts of antibodies in the peripheral circulation. Thus, in contrast to intravenous and subcutaneous delivery, intrathecal administration is an effective and reliable way to target CNS antigens. Our data reveal that antibody delivery to the CNS is far from trivial. While intrathecal application is feasible and guarantees defined antibody doses in the effective range for a biological function, the identification and establishment of easier routes of administration remains an important task to facilitate antibody-based future therapies of CNS disorders.

Publication status

published

Editor

Book title

Volume

17 (3)

Pages / Article No.

1153 - 1159

Publisher

Springer

Event

Edition / version

Methods

Software

Geographic location

Date collected

Date created

Subject

CNS antibody delivery; Stroke; Intrathecal; Functional recovery; Anti-Nogo antibody therapy

Organisational unit

Notes

Funding

294115 - The Nogo-A receptor complex after CNS injury and its role in the developing and adult nervous system (EC)

Related publications and datasets