Stimulated-single fiber electromyography monitoring of anti-sense induced changes in experimental autoimmune myasthenia gravis.
The neuromuscular weakness associated with myasthenia gravis (MG) can be transiently relieved by pharmacological inhibitors of acetylcholinesterase (AChE). Here, we expand the anticholinesterase repertoire to include 2'-O-methyl-protected antisense oligonucleotides targeted to AChE mRNA (EN101). Using stimulated-single fiber electromyography, we show that EN101 treatment of rats with experimental autoimmune myasthenia gravis (EAMG), improved the mean consecutive difference (MCD) and blocking for 24h. This treatment was more efficient than pyridostigmine and was accompanied by marked improvement in stamina and clinical profile.
Boneva
Neli
N
Laboratory of Neuroimmunology, Department of Neurology, and the Agnes Ginges Center for Human Neurogenetics, Hadassah University Hospital and Hebrew University Medical School, Jerusalem.
Hamra-Amitay
Yasmine
Y
Wirguin
Itzhak
I
Brenner
Talma
T
D000110:Acetylcholinesterase / Q000235:genetics; D000818:Animals; D004558:Electric Stimulation / Q000379:methods; D004576:Electromyography; D005080:Exercise Test / Q000379:methods; D005260:Female; D008991:Monitoring, Physiologic; D009132:Muscles / Q000187:drug effects / Q000503:physiopathology* / Q000528:radiation effects; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology*; D009469:Neuromuscular Junction / Q000187:drug effects / Q000503:physiopathology / Q000528:radiation effects; D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D011950:Receptors, Cholinergic / Q000276:immunology; D013997:Time Factors
C477243:EN101; D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D011950:Receptors, Cholinergic; D000110:Acetylcholinesterase