title: Effect of EPI-743 on the clinical course of the mitochondrial disease Leber hereditary optic neuropathy.
abstract: OBJECTIVE
  To evaluate the safety and efficacy of a new therapeutic agent, EPI-743, in Leber hereditary optic neuropathy (LHON) using standard clinical, anatomic, and functional visual outcome measures.
  
  
  METHODS
  Open-label clinical trial.
  
  
  METHODS
  University medical center. Patients  Five patients with genetically confirmed LHON with acute loss of vision were consecutively enrolled and treated with the experimental therapeutic agent EPI-743 within 90 days of conversion. Intervention  During the course of the study, 5 consecutive patients received EPI-743, by mouth, 3 times daily (100-400 mg per dose).
  
  
  METHODS
  Treatment effect was assessed by serial measurements of anatomic and functional visual indices over 6 to 18 months, including Snellen visual acuity, retinal nerve fiber layer thickness measured by optical coherence tomography, Humphrey visual fields (mean decibels and area with 1-log unit depression), and color vision. Treatment effect in this clinical proof of principle study was assessed by comparison of the prospective open-label treatment group with historical controls.
  
  
  RESULTS
  Of 5 subjects treated with EPI-743, 4 demonstrated arrest of disease progression and reversal of visual loss. Two patients exhibited a total recovery of visual acuity. No drug-related adverse events were recorded.
  
  
  CONCLUSIONS
  In a small open-label trial, EPI-743 arrested disease progression and reversed vision loss in all but 1 of the 5 consecutively treated patients with LHON. Given the known natural history of acute and rapid progression of LHON resulting in chronic and persistent bilateral blindness, these data suggest that the previously described irreversible priming to retinal ganglion cell loss may be reversed.
authors.affiliation: Doheny Eye Institute, Department of Ophthalmology, USC-Keck School of Medicine, 1450 San Pablo St, Los Angeles, CA 90089-0228, USA. asadun@usc.edu
authors.forename: Alfredo A
authors.initials: AA
authors.lastname: Sadun
authors.forename: Carlos Filipe
authors.initials: CF
authors.lastname: Chicani
authors.forename: Fred N
authors.initials: FN
authors.lastname: Ross-Cisneros
authors.forename: Piero
authors.initials: P
authors.lastname: Barboni
authors.forename: Martin
authors.initials: M
authors.lastname: Thoolen
authors.forename: William D
authors.initials: WD
authors.lastname: Shrader
authors.forename: Kenneth
authors.initials: K
authors.lastname: Kubis
authors.forename: Valerio
authors.initials: V
authors.lastname: Carelli
authors.forename: Guy
authors.initials: G
authors.lastname: Miller
mesh_terms: D000293:Adolescent; D001766:Blindness / Q000209:etiology / Q000517:prevention & control; D002648:Child; D002851:Chromatography, High Pressure Liquid; D055253:Color Vision; D017277:Drug Approval; D004632:Emergency Medical Services; D005123:Eye / Q000473:pathology; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D028361:Mitochondrial Diseases / Q000150:complications; D029242:Optic Atrophy, Hereditary, Leber / Q000188:drug therapy* / Q000235:genetics; D012160:Retina / Q000473:pathology; D053719:Tandem Mass Spectrometry; D041623:Tomography, Optical Coherence; D014451:Ubiquinone / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D014481:United States; D014486:United States Food and Drug Administration; D014792:Visual Acuity; D058609:Visual Field Tests; D055815:Young Adult
chemical_list: D014451:Ubiquinone; C571746:alpha-tocotrienol quinone