Emory University

University of Florida Research Foundation Inc

David B Rye

Andrew Jenkins

Kathy P Parker

Lyndon Lien

Gary J Bassell

Maurice Scott Swanson

Eric Tzy-Shi Wang

Disclosed are methods of treating a disorder or disease associated with myotonic dystrophy. Methods of treating a CNS dysfunction and/or cognitive impairment associated with myotonic dystrophy in a subject comprising administering a therapeutically effective amount of a GABAA receptor antagonist or inverse agonist to the subject are disclosed. Methods of treating a myotonic dystrophy associated disease or disorder caused by mis-splicing of GABRG2 in a subject comprising administering a therapeutically effective amount of a GABAA receptor antagonist or inverse agonist to the subject are disclosed. Methods of improving cognitive function or alertness in a subject having myotonic dystrophy comprising administering a therapeutically effective amount of a GABAA receptor antagonist or inverse agonist to the subject are disclosed. Examples of the GABAA receptor antagonist or inverse agonist include flumazenil, clarithromycin, a fluoroquinolone, picrotoxin, bicuculline, gabazine, cicutoxin, oenan-thotoxin, pentylenetetrazol, Ro15-4513, sarmazenil, amentoflavone, zinc, and any combination thereof.

Treatment of conditions associated with myotonic dystrophy

GABAreceptor mediated hypersomnia can be treated by administering a GABAreceptor antagonist (e.g., flumazenil; clarithromycin; picrotoxin; bicuculline; cicutoxin; and oenanthotoxin). In some embodiments, the GABAreceptor antagonist is flumazenil or clarithromycin. The GABAreceptor mediated hypersomnia includes shift work sleep disorder, obstructive sleep apnea/hypopnea syndrome, narcolepsy, excessive sleepiness, hypersomnia (e.g., idiopathic hypersomnia; recurrent hypersomnia; endozepine related recurrent stupor; and amphetamine resistant hypersomnia), and excessive sleepiness associated with shift work sleep disorder, obstructive sleep apnea/hypopnea syndrome, and hypersomnia (e.g., idiopathic hypersomnia; recurrent hypersomnia; endozepine related recurrent stupor; and amphetamine resistant hypersomnia.

Use of GABAreceptor antagonists for the treatment of excessive sleepiness and disorders associated with excessive sleepiness

GABAreceptor mediated hypersomnia can be treated by administering a GABAreceptor antagonist (e.g., flumazenil; clarithromycin; picrotoxin; bicuculline; cicutoxin; and oenanthotoxin). In some embodiments, the GABAreceptor antagonist is flumazenil or clarithromycin. The GABAreceptor mediated hypersomnia includes shift work sleep disorder, obstructive sleep apnea/hypopnea syndrome, narcolepsy, excessive sleepiness, hypersomnia (e.g., idiopathic hypersomnia; recurrent hypersonmia; endozepine related recurrent stupor; and amphetamine resistant hypersonmia), and excessive sleepiness associated with shift work sleep disorder, obstructive sleep apnea/hypopnea syndrome, and hypersomnia (e.g., idiopathic hypersomnia; recurrent hypersomnia; endozepine related recurrent stupor; and amphetamine resistant hypersomnia.

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Dunwoody, GA, United States of America

David B Rye