Intratympanic treatment of acute acoustic trauma with a cell-permeable JNK ligand: a prospective randomized phase I/II study.
OBJECTIVE
Intratympanic administration of a cell-permeable JNK ligand has been shown to prevent hearing loss after acute acoustic trauma in animal models.


CONCLUSIONS
Functional and morphological analysis of the treated ears revealed that AM-111 had an excellent otoprotective effect, even when administered hours after the noise exposure. Blocking the signal pathway with D-JNKI-1 is therefore a promising way to protect the morphological integrity and physiological function of the inner ear in various conditions involving acute sensorineural hearing loss.


METHODS
For the first application of AM-111 in humans, we organized a clinical phase I/II trial in patients with acute acoustic trauma after exposure to firecrackers in Berlin and Munich on New Year's Eve 2005/2006. We randomly selected 11 patients for intratympanic treatment with AM-111 at a concentration of 0.4 mg/ml or 2 mg/ml within 24 h after noise exposure. Pure tone audiometry and otoacoustic emissions were assessed before treatment and on days 3 and 30 thereafter.


RESULTS
Based on clinical experience and on a calculation using an empirically derived exponential hearing recovery function AM-111 seems to have had a therapeutic effect. A total of 13 adverse events were reported in 5 study participants. None of the adverse events were serious or severe.
Suckfuell
M
M
Ludwig-Maximilians-Universität München, München, Germany. markus.suckfuell@med.uni-muenchen.de
Canis
M
M
Strieth
S
S
Scherer
H
H
Haisch
A
A
D000208:Acute Disease; D000328:Adult; D001301:Audiometry, Pure-Tone; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D006317:Hearing Loss, Noise-Induced / Q000517:prevention & control*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000627:therapeutic use*; D011446:Prospective Studies; D020127:Recovery of Function / Q000187:drug effects
D004791:Enzyme Inhibitors; D010455:Peptides; D048031:JNK Mitogen-Activated Protein Kinases; C478085:D-JNKI-1