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Gerber YN, Privat A, Perrin FE. Gacyclidine improves the survival and reduces motor deficits in a mouse model of amyotrophic lateral sclerosis. Front Cell Neurosci. 2013;7:280doi: 10.3389/fncel.2013.00280.
Gerber, Y. N., Privat, A., & Perrin, F. E. (2013). Gacyclidine improves the survival and reduces motor deficits in a mouse model of amyotrophic lateral sclerosis. Frontiers in cellular neuroscience, 7280. https://doi.org/10.3389/fncel.2013.00280
Gerber, Yannick N, et al. "Gacyclidine improves the survival and reduces motor deficits in a mouse model of amyotrophic lateral sclerosis." Frontiers in cellular neuroscience vol. 7 (2013): 280. doi: https://doi.org/10.3389/fncel.2013.00280
Gerber YN, Privat A, Perrin FE. Gacyclidine improves the survival and reduces motor deficits in a mouse model of amyotrophic lateral sclerosis. Front Cell Neurosci. 2013 Dec 27;7:280. doi: 10.3389/fncel.2013.00280. eCollection 2013. PMID: 24409117; PMCID: PMC3873512.
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Front Cell Neurosci. 2013 Dec 27;7:280. doi: 10.3389/fncel.2013.00280. eCollection 2013.

Gacyclidine improves the survival and reduces motor deficits in a mouse model of amyotrophic lateral sclerosis.

Frontiers in cellular neuroscience

Yannick N Gerber, Alain Privat, Florence E Perrin

Affiliations

  1. Institute for Neurosciences of Montpellier (INM), INSERM U 1051 Montpellier, France ; "Integrative Biology of Neurodegeneration," IKERBASQUE Basque Foundation for Science, Neuroscience Department, University of the Basque Country Bilbao, Spain.
  2. Institute for Neurosciences of Montpellier (INM), INSERM U 1051 Montpellier, France.
  3. Institute for Neurosciences of Montpellier (INM), INSERM U 1051 Montpellier, France ; "Integrative Biology of Neurodegeneration," IKERBASQUE Basque Foundation for Science, Neuroscience Department, University of the Basque Country Bilbao, Spain ; "Integrative Biology of Neuroregeneration," Faculty of Science, University of Montpellier 2 Montpellier, France.

PMID: 24409117 PMCID: PMC3873512 DOI: 10.3389/fncel.2013.00280

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder typified by a massive loss of motor neurons with few therapeutic options. The exact cause of neuronal degeneration is unknown but it is now admitted that ALS is a multifactorial disease with several mechanisms involved including glutamate excitotoxicity. More specifically, N-methyl-D-aspartate (NMDA)-mediated cell death and impairment of the glutamate-transport has been suggested to play a key role in ALS pathophysiology. Thus, evaluating NMDAR antagonists is of high therapeutic interest. Gacyclidine, also named GK11, is a high affinity non-competitive NMDAR antagonist that may protect against motor neuron death in an ALS context. Moreover, GK11 presents a low intrinsic neurotoxicity and has already been used in two clinical trials for CNS lesions. In the present study, we investigated the influence of chronic administration of two doses of GK11 (0.1 and 1 mg/kg) on the survival and the functional motor activity of hSOD1(G93A) mice, an animal model of ALS. Treatment started at early symptomatic age (60 days) and was applied bi-weekly until the end stage of the disease. We first confirmed that functional alteration of locomotor activity was evident in the hSOD1(G93A) transgenic female mice by 60 days of age. A low dose of GK11 improved the survival of the mice by 4.3% and partially preserved body weight. Improved life span was associated with a delay in locomotor function impairment. Conversely, the high dose treatment worsened motor functions. These findings suggest that chronic administration of GK11 beginning at early symptomatic stage may be beneficial for patients with ALS.

Keywords: ALS; GK11; NMDA receptor antagonist; locomotion; survival

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