Save
ABT-555, a human anti-RGMa monoclonal antibody promotes axon regeneration and neuroprotection in multiple sclerosis models
Author(s): ,
B.K. Mueller
Affiliations:
AbbVie Inc., Ludwigshafen, Germany
,
Y. Cui
Affiliations:
AbbVie Inc., Ludwigshafen, Germany
,
L. Huang
Affiliations:
AbbVie Biotherapeutics, Worcester, MA
,
S. Greenberg
Affiliations:
AbbVie Biotherapeutics, Redwood City, CA, United States
H. Schoemaker
Affiliations:
AbbVie Inc., Ludwigshafen, Germany
ECTRIMS Online Library. Mueller B. Oct 8, 2015; 115435; 350
Bernhard Mueller
Bernhard Mueller
Login now to access Regular content available to all registered users.

You may also access this content "anytime, anywhere" with the Free MULTILEARNING App for iOS and Android
Abstract
Discussion Forum (0)
Rate & Comment (0)
Abstract: P582

Type: Poster

Abstract Category: Neurorepair

Summary: Repulsive Guidance Molecule a (RGMa) is a potent inhibitor of axon regeneration and remyelination and is involved in neuronal cell death. In addition RGMa plays an important role in neuroinflammation. Targeting RGMa by the selective antibody ABT-555 promotes axon regeneration, enhances neuroprotection, stimulates remyelination and decreases microglial inflammation.

Objective: To present the preclinical data of ABT-555 in several different MS-related animal models.

Methods: Anti-RGMa antibodies, including ABT-555, were evaluated in a rat spinal cord targeted experimental autoimmune encephalitis (tEAE) model induced by myelin oligodendrocyte glycoprotein (MOG)-sensitization followed by local injection of tumor necrosis factor-beta (TNF)-b and gamma interferon (IFN)-g; in an optic neuritis model using the same protocol of MOG sensitization; and in a mouse MOG disseminated EAE model (dEAE) immunized with MOG in complete Freund´s adjuvant and boosted with pertussis toxin.

Results: Administration of ABT-555 accelerated functional recovery in both EAE models, enhanced axonal regeneration within inflammatory lesions, and stimulated remyelination. Treatment with RGMa antibodies also decreased the inflammatory signal by CD68+ cells within the spinal cord. ABT-555 stimulated regenerative axon growth within the inflammatory optic nerve lesion in a dose dependent manner on immunohistochemistry (IHC) and reduced degeneration of the retinal nerve fiber layer measured using optical coherence tomography (OCT), proving its potent neuroprotective efficacy .

Conclusions: The specific targeting of RGMa by ABT-555 in several animal models of autoimmune inflammatory disease of the CNS resulted in immune modulation and neuroprotection and neuroregeneration and this new therapeutic strategy may provide novel benefit in patients with MS and warrants further study. The early clinical evaluation of ABT-555 in healthy volunteers and MS patients is currently underway.

Disclosure: All authors are employees of AbbVie. The design, study conduct, and financial support for this research was provided by AbbVie. AbbVie participated in the interpretation of data, review, and approval of the publication.

Code of conduct/disclaimer available in General Terms & Conditions
Anonymous User Privacy Preferences

Strictly Necessary Cookies (Always Active)

MULTILEARNING platforms and tools hereinafter referred as “MLG SOFTWARE” are provided to you as pure educational platforms/services requiring cookies to operate. In the case of the MLG SOFTWARE, cookies are essential for the Platform to function properly for the provision of education. If these cookies are disabled, a large subset of the functionality provided by the Platform will either be unavailable or cease to work as expected. The MLG SOFTWARE do not capture non-essential activities such as menu items and listings you click on or pages viewed.


Performance Cookies

Performance cookies are used to analyse how visitors use a website in order to provide a better user experience.



Google Analytics is used for user behavior tracking/reporting. Google Analytics works in parallel and independently from MLG’s features. Google Analytics relies on cookies and these cookies can be used by Google to track users across different platforms/services.


Save Settings