Title |
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
|
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Published in |
Journal of Molecular Neuroscience, December 2015
|
DOI | 10.1007/s12031-015-0695-2 |
Pubmed ID | |
Authors |
Chen Benkler, Yael Barhum, Tali Ben-Zur, Daniel Offen |
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. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 41 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 10 | 24% |
Student > Master | 8 | 20% |
Student > Bachelor | 7 | 17% |
Researcher | 3 | 7% |
Student > Doctoral Student | 3 | 7% |
Other | 4 | 10% |
Unknown | 6 | 15% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 11 | 27% |
Medicine and Dentistry | 9 | 22% |
Biochemistry, Genetics and Molecular Biology | 6 | 15% |
Neuroscience | 4 | 10% |
Pharmacology, Toxicology and Pharmaceutical Science | 2 | 5% |
Other | 2 | 5% |
Unknown | 7 | 17% |