The monoclonal antibody GNbAC1: targeting human endogenous retroviruses in multiple sclerosis.
- 2019-03-16
Published in:
- Therapeutic advances in neurological disorders. - 2019
GNbAC1
human endogenous retrovirus
monoclonal antibody
progressive multiple sclerosis
relapsing multiple sclerosis
English
Background
Multiple sclerosis (MS) is an autoimmune demyelinating disorder of the central nervous system (CNS). Despite improvements of immunomodulatory therapies in relapsing-remitting MS, the pathomechanisms of progressive disease are poorly understood and therapeutically addressed to date. A pathophysiological role for proteins encoded by human endogenous retroviruses (HERVs) has been proposed. GNbAC1 is a monoclonal antibody directed against the envelope protein of a HERV with postulated involvement in MS.
Methods
This review addresses the treatment concept of GNbAC1, the design, preclinical and clinical development of the antibody, as published by November 2018. All four in-human trials (of which two addressed MS) are discussed.
Conclusion
The treatment concept of GNbAC1 is appealing but remains controversial due to conflicting results regarding the hypothesized underlying pathomechanism. Anticipated immunomodulatory effects were not observed in clinical or pharmacodynamic analyses of the currently available data. However, a magnetic resonance imaging sign compatible with the remyelinating potential of GNbAC1 encouraged further development of this antibody in progressive MS. No relevant issues with tolerability or safety have been described to date.
Multiple sclerosis (MS) is an autoimmune demyelinating disorder of the central nervous system (CNS). Despite improvements of immunomodulatory therapies in relapsing-remitting MS, the pathomechanisms of progressive disease are poorly understood and therapeutically addressed to date. A pathophysiological role for proteins encoded by human endogenous retroviruses (HERVs) has been proposed. GNbAC1 is a monoclonal antibody directed against the envelope protein of a HERV with postulated involvement in MS.
Methods
This review addresses the treatment concept of GNbAC1, the design, preclinical and clinical development of the antibody, as published by November 2018. All four in-human trials (of which two addressed MS) are discussed.
Conclusion
The treatment concept of GNbAC1 is appealing but remains controversial due to conflicting results regarding the hypothesized underlying pathomechanism. Anticipated immunomodulatory effects were not observed in clinical or pharmacodynamic analyses of the currently available data. However, a magnetic resonance imaging sign compatible with the remyelinating potential of GNbAC1 encouraged further development of this antibody in progressive MS. No relevant issues with tolerability or safety have been described to date.
- Language
-
- English
- Open access status
- gold
- Identifiers
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- DOI 10.1177/1756286419833574
- PMID 30873219
- Persistent URL
- https://sonar.ch/global/documents/231614
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