Therapeutic immunization with a glatiramer acetate derivative does not alter survival in G93A and G37R SOD1 mouse models of familial ALS

Haenggeli, Christine; Julien, J.P.; Mosley, R. Lee; Perez, Natalie; Dhar, Alok; Gendelman, Howard E.; Rothstein, Jeffrey D.

doi:10.1016/j.nbd.2006.12.013

Cited by 41 publications

(25 citation statements)

References 28 publications

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“…Preliminary experiments suggest that mutant SOD1 may also interfere with microglia expression of IGF-1 (data not shown). Immunization with glatiramer acetate, thought to induce dendritic-like IGF1ϩ microglia, was effective in an Alzheimer disease model (24), but not mutant SOD1 mice (33). Failure may be due to insensitivity from preexisting neuroprotective activity, or to decreased microglia viability (32).…”

Section: Discussionmentioning

confidence: 99%

T lymphocytes potentiate endogenous neuroprotective inflammation in a mouse model of ALS

Chiu¹,

Chen

Zheng³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

308

303

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Section: Discussionmentioning

confidence: 99%

T lymphocytes potentiate endogenous neuroprotective inflammation in a mouse model of ALS

Chiu¹,

Chen

Zheng³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

308

303

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“…Likewise, active vaccination with misfolded mutant superoxide dismutase 1 (SOD-1) in a familial amyotrophic lateral sclerosis mouse model carrying an SOD-1 mutation reduced loss of spinal cord neurons and caused a modest but statistically significant increase in life expectancy (Urushitani et al 2007). Some benefits of nonspecific active vaccinations with Copaxone-based regimens have been reported (Angelov et al 2003, Benner et al 2004 in ALS and Parkinson models, although safety concerns have been raised (Haenggeli et al 2007). The effects of passive vaccination approaches to these diseases have not been reported to our knowledge, but this clearly represents an avenue for future research.…”

Section: Parkinson Disease and Amyotrophic Lateral Sclerosismentioning

confidence: 99%

Active and Passive Immunotherapy for Neurodegenerative Disorders

Brody

Holtzman

2008

Annu. Rev. Neurosci.

229

202

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Immunotherapeutic strategies to combat neurodegenerative disorders have galvanized the scientific community since the first dramatic successes in mouse models recreating aspects of Alzheimer disease (AD) were reported. However, initial human trials of active amyloid-beta (Aβ) vaccination were halted early because of a serious safety issue: meningoencephalitis in 6% of subjects. Nonetheless, some encouraging preliminary data were obtained, and rapid progress has been made toward developing alternative, possibly safer active and passive immunotherapeutic approaches for several neurodegenerative conditions. Many of these are currently in human trials for AD. Despite these advances, our understanding of the essential mechanisms underlying the effects seen in preclinical models and human subjects is still incomplete. Antibody-induced phagocytosis of pathological protein deposits, direct antibody-mediated disruption of aggregates, neutralization of toxic soluble proteins, a shift in equilibrium toward efflux of specific proteins from the brain, cellmediated immune responses, and other mechanisms may all play roles depending on the specific immunotherapeutic scenario.

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“…Here, our results demonstrate declines in rotarod performance in G37R male mice by 30 weeks of age, the maximum age at which behavioral results are available for these mice, corresponding to 15 weeks of age with SG exposure. Earlier reports have shown late (40 -50 weeks of age) declines in rotarod performance of G37R mice [35,36]. In contrast, preferential motor unit loss from fast-twitch muscles [4,37] and the initiation of the denervation process of motor endplates [2] start earlier, before the onset of disease symptoms in G93A mice.…”

Section: Discussionmentioning

confidence: 90%

Early Exposure to Environmental Toxin Contributes to Neuronal Vulnerability and Axonal Pathology in a Model of Familial ALS

Lee¹,

Shaw²

2012

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Adult onset amyotrophic lateral sclerosis (ALS) arises due to progressive and irreversible functional deficits to the central nervous system, specifically the loss of motor neurons. Sporadic ALS causality is not well understood, but is almost certainly of multifactorial origin involving a combination of genetic and environmental factors. The discovery of endemic ALS in the native Chamorro population of Guam during the 1950s and the co-occurrence of Parkinsonism and dementia in some patients led to searches for environmental toxins that could be responsible. In the present paper, we report that an environmental neurotoxin enhances mutant superoxide dismutase (SOD)-induced spinal motor neuron death and pathology and induces motor axon abnormalities. These results cumulatively confirm earlier findings that exposure to an environmental toxin is sufficient to produce the disease phenotype and indicate a role for gene-environment interaction in some forms of the disease.

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Therapeutic immunization with a glatiramer acetate derivative does not alter survival in G93A and G37R SOD1 mouse models of familial ALS

Cited by 41 publications

References 28 publications

T lymphocytes potentiate endogenous neuroprotective inflammation in a mouse model of ALS

T lymphocytes potentiate endogenous neuroprotective inflammation in a mouse model of ALS

Active and Passive Immunotherapy for Neurodegenerative Disorders

Early Exposure to Environmental Toxin Contributes to Neuronal Vulnerability and Axonal Pathology in a Model of Familial ALS

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