Multifactorial Gene Therapy Enhancing the Glutamate Uptake System and Reducing Oxidative Stress Delays Symptom Onset and Prolongs Survival in the SOD1-G93A ALS Mouse Model.
J Mol Neurosci
; 58(1): 46-58, 2016 Jan.
Article
em En
| MEDLINE
| ID: mdl-26691332
ABSTRACT
The 150-year-long search for treatments of amyotrophic lateral sclerosis (ALS) is still fueled by frustration over the shortcomings of available therapeutics. Contributing to the therapeutic limitations might be the targeting of a single aspect of this multifactorial-multisystemic disease. In an attempt to overcome this, we devised a novel multifactorial-cocktail treatment, using lentiviruses encoding EAAT2, GDH2, and NRF2, that act synergistically to address the band and width of the effected excito-oxidative axis, reducing extracellular-glutamate and glutamate availability while improving the metabolic state and the anti-oxidant response. This strategy yielded particularly impressive results, as all three genes together but not separately prolonged survival in ALS mice by an average of 19-22 days. This was accompanied by improvement in every parameter evaluated, including body-weight loss, reflex score, neurologic score, and motor performance. We hope to provide a novel strategy to slow down disease progression and alleviate symptoms of patients suffering from ALS.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Superóxido Dismutase
/
Terapia Genética
/
Estresse Oxidativo
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Ácido Glutâmico
/
Proteínas de Transporte de Glutamato da Membrana Plasmática
/
Esclerose Lateral Amiotrófica
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Mol Neurosci
Assunto da revista:
BIOLOGIA MOLECULAR
/
NEUROLOGIA
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Israel