Presymptomatic treatment with acetylcholinesterase antisense oligonucleotides prolongs survival in ALS (G93A-SOD1) mice

Gotkine Marc, Rozenstein Leah, Einstein Ofira, Abramsky Oded, Argov Zohar, Rosenmann Hanna

Research output: Contribution to journalArticlepeer-review

Abstract

Objective. Previous research suggests that acetylcholinesterase (AChE) may be involved in ALS pathogenesis. AChE enzyme inhibitors can upregulate AChE transcription which in certain contexts can have deleterious (noncatalytic) effects, making them theoretically harmful in ALS, whilst AChE antisense-oligonucleotides (mEN101), which downregulate AChE may be beneficial. Our aim was to investigate whether downregulation of AChE using mEN101 is beneficial in an ALS mouse model. Methods. ALS (G93A-SOD1) mice received saline, mEN101, inverse-EN101, or neostigmine. Treatments were administered from 5 weeks. Disease-onset and survival were recorded. Additional mice were sacrificed for pathological analysis at 15 weeks of age. In a follow-up experiment treatment was started at the symptomatic stage at a higher dose. Results. mEN101 given at the presymptomatic (but not symptomatic) stage prolonged survival and attenuated motor-neuron loss in ALS mice. In contrast, neostigmine exacerbated the clinical parameters. Conclusions. These results suggest that AChE may be involved in ALS pathogenesis. The accelerated disease course with neostigmine suggests that any beneficial effects of mEN101 occur through a non-catalytic rather than cholinergic mechanism.

Original languageEnglish
Article number845345
JournalBioMed Research International
Volume2013
DOIs
StatePublished - 2013
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General Immunology and Microbiology
  • General Biochemistry,Genetics and Molecular Biology

Fingerprint

Dive into the research topics of 'Presymptomatic treatment with acetylcholinesterase antisense oligonucleotides prolongs survival in ALS (G93A-SOD1) mice'. Together they form a unique fingerprint.

Cite this