GSK249320, A Monoclonal Antibody Against the Axon Outgrowth Inhibition Molecule Myelin-Associated Glycoprotein, Improves Outcome of Rodents with Experimental Stroke

@article{Cash2016GSK249320AM,
  title={GSK249320, A Monoclonal Antibody Against the Axon Outgrowth Inhibition Molecule Myelin-Associated Glycoprotein, Improves Outcome of Rodents with Experimental Stroke},
  author={D. Cash and A. Easton and M. Mesquita and J. Beech and S. Williams and Andrew Lloyd and E. Irving and S. Cramer},
  journal={Journal of neurology and experimental neuroscience},
  year={2016},
  volume={2},
  pages={28 - 33}
}
Myelin-associated glycoprotein (MAG) is an inhibitor of axon growth. MAG levels increase after stroke. GSK249320 is a monoclonal antibody that neutralizes MAG-mediated inhibition and so may promote axon outgrowth and improve post-stroke outcomes. The current study tested the hypothesis that GSK249320 initiated 24 hours or 7 days after experimental stroke improves behavioural outcomes. Rats with right middle cerebral artery occlusion for 90 minutes were randomized to receive 6 weeks of… Expand
Proof-of-Concept Randomized Trial of the Monoclonal Antibody GSK249320 Versus Placebo in Stroke Patients
TLDR
GSK249320, within 72 hours of stroke, demonstrated no improvement on gait velocity compared with placebo, findings potentially useful to future studies aiming to use a monoclonal antibody to modify activity in specific biological pathways to improve recovery from stroke. Expand
Inflammation and Stem Cell Therapy for Stroke
TLDR
It is found that in vitro-derived anti-inflammatory (M2- like) MDM delivered into CSF migrate into ischemic cortex, maintain their M2-like phenotype, and most importantly, improve recovery of motor and cognitive function in stroke-subjected mice without influencing infarct volume. Expand
Monoclonal antibody as an emerging therapy for acute ischemic stroke.
TLDR
This review will focus on recent advances on AIS therapy by using mAb that targets the signaling cascades and endogenous molecules such as inflammation, growth factors, acid-sensing ion channels, and N-methyl-D-aspartate receptors. Expand
Pharmacological Enhancement of Stroke Recovery
TLDR
Various drugs, including modulators of neurotransmitters, axonal growth inhibitor blockers, and growth factors, have been examined in preclinical and clinical studies for their ability to promote neural repair, particularly in the motor system. Expand
Enhancing Plasticity of the Central Nervous System: Drugs, Stem Cell Therapy, and Neuro-Implants
TLDR
A review of novel drug therapies with strong potential in the clinic for functional recovery after stroke and new avenues of stem cell therapy in patients with a cerebral lesion are discussed. Expand
Delivery of neurotrophic factors in the treatment of age-related chronic neurodegenerative diseases
TLDR
This review covers the various mechanisms of neurodegeneration, its molecular link with aging, different neurotrophic factor classes and their potentials, current treatment strategies, the challenges associated with the delivery of neurotrophic factors, administration routes, design of different delivery vehicle design, alternative modalities of delivery, and the clinical translational challenges of these strategies. Expand
Functions and therapeutic targets of Siglec-mediated infections, inflammations and cancers.
TLDR
Amplifying or eliminating the SA-Siglec interactions is a promising strategy to treat cancers, infections and inflammations, based on SA modifications in different linkages or nanoparticle decoration, and on the antibodies in conjugation of chimeric receptor design or toxins. Expand

References

SHOWING 1-10 OF 28 REFERENCES
Antibodies to myelin‐associated glycoprotein accelerate preferential motor reinnervation
TLDR
Antibody administration has a generalized effect on sensory regeneration that is unrelated to the behavior of motoneurons in the same nerve, and blocking access to MAG in the distal nerve stump thus accelerated and enhanced PMR. Expand
Overcoming inhibitors in myelin to promote axonal regeneration
TLDR
It is reported that artificially increasing cAMP levels in older neurons can alter their growth-state and induce axonal growth in the presence of myelin-associated inhibitors. Expand
Identification of Neuroprotective Properties of Anti-MAG Antibody: A Novel Approach for the Treatment of Stroke?
  • E. Irving, M. Vinson, +9 authors A. A. Parsons
  • Medicine
  • Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
  • 2005
TLDR
The novel finding that an anti-MAG monoclonal antibody not only possesses the ability to neutralise the inhibitory effect of MAG on neurons but also directly protects oligodendrocytes from glutamate-mediated oxidative stress-induced cell death is reported here. Expand
Targeting the Nogo-A signalling pathway to promote recovery following acute CNS injury.
TLDR
In vivo findings have been shown to significantly enhance axonal regeneration and neuroplasticity leading to improved functional recovery in animal models of acute CNS injury, providing a sound basis for the development of an effective treatment for acute CNS injuries in humans. Expand
Nogo Receptor Antagonism Promotes Stroke Recovery by Enhancing Axonal Plasticity
TLDR
Delayed pharmacological blockade of the NgR promotes subacute stroke recovery by facilitating axonal plasticity in rats with middle cerebral artery occlusion and in Mutant mice lacking NgR or Nogo-AB. Expand
Targeting the Nogo-A Signalling Pathway to Promote Recovery Following Acute CNS Injury
TLDR
In vivo findings provide a sound basis for the development of an effective treatment for acute CNS injuries in humans and significantly enhance axonal regeneration and neuroplasticity leading to improved functional recovery in animal models of acute CNS injury. Expand
Growth-associated gene and protein expression in the region of axonal sprouting in the aged brain after stroke
TLDR
The aged brain does not simply have a reduction in growth-associated molecules after stroke, but a completely unique molecular profile of post-stroke axonal sprouting. Expand
Combination of NEP 1-40 Treatment and Motor Training Enhances Behavioral Recovery After a Focal Cortical Infarct in Rats
TLDR
This study suggests that behavioral training interacts with the effects of the axonal growth promoter, NEP 1-40, and may accelerate behavioral recovery after focal cortical ischemia. Expand
A novel role for myelin-associated glycoprotein as an inhibitor of axonal regeneration
TLDR
It is demonstrated that the myelin-associated glycoprotein (MAG), a transmembrane protein of both CNS and PNS myelin, strongly inhibits neurite outgrowth from both developing cerebellar and adult dorsal root ganglion (DRG) neurons in vitro and is reversed by an anti-MAG antibody. Expand
Tissue sparing and functional recovery following experimental traumatic brain injury is provided by treatment with an anti‐myelin‐associated glycoprotein antibody
TLDR
Results indicate that MAG may contribute to the pathophysiology of experimental TBI and treatment strategies that target MAG may be suitable for further evaluation. Expand
...
1
2
3
...