title: Tolerability and Safety of Combined Glatiramer Acetate and N-Acetylcysteine in Relapsing-Remitting Multiple Sclerosis.
abstract: BACKGROUND
  Multiple sclerosis (MS) is an autoimmune disorder of the central nervous system where inflammation and neurodegeneration play key roles. Mounting evidence implicates oxidative stress in the development of irreversible neuronal and glial injury in this condition. N-acetylcysteine (NAC) is a sulfhydryl amino acid derivative with antioxidant and antiapoptotic properties. Administration of NAC to mice attenuated the induction of or improved experimental autoimmune encephalomyelitis (an MS model).
  
  
  METHODS
  We performed an open-label study to explore the tolerability and safety of the combination of glatiramer acetate (GA) and NAC in patients with relapsing-remitting multiple sclerosis at the outpatient MS clinics of the Jewish General Hospital and Hôpital Charles Lemoyne, Montreal, Canada. Seven patients with relapsing-remitting multiple sclerosis with at least one T1 gadolinium-enhancing lesion on screening magnetic resonance imaging were recruited. Treatment consisted of a 10-week run-in period followed by 36-week treatment with a combination of GA 20 mg subcutaneously once daily plus NAC 2.5 g orally twice daily. Outcome measures included safety and tolerability, redox biochemistry, and magnetic resonance imaging effect.
  
  
  RESULTS
  Treatment with the combination of GA and NAC was safe and well tolerated.
  
  
  CONCLUSIONS
  In light of the favorable safety profile, an efficacy-demonstrating study may be considered.
authors.affiliation: Departments of *Neurology and Neurosurgery, and †Medicine (Geriatrics), McGill University; ‡Lady Davis Institute for Medical Research, Jewish GeneralHospital; §NeuroRx Research; ∥Hôpital Charles Lemoyne; ¶Department of Radiology, Jewish General Hospital; and #Teva Neuroscience Canada, Montreal,Quebec, Canada.
authors.forename: Hyman M
authors.initials: HM
authors.lastname: Schipper
authors.forename: Douglas
authors.initials: D
authors.lastname: Arnold
authors.forename: Francois
authors.initials: F
authors.lastname: GrandʼMaison
authors.forename: Calvin
authors.initials: C
authors.lastname: Melmed
authors.forename: Fraser
authors.initials: F
authors.lastname: Moore
authors.forename: Mark
authors.initials: M
authors.lastname: Levental
authors.forename: Haixiang
authors.initials: H
authors.lastname: Su
authors.forename: Michel
authors.initials: M
authors.lastname: Constantin
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Stril
authors.forename: Jean
authors.initials: J
authors.lastname: Godin
mesh_terms: D000111:Acetylcysteine / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D000068717:Glatiramer Acetate / Q000627:therapeutic use*; D005978:Glutathione / Q000097:blood; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000188:drug therapy*; D017063:Outcome Assessment, Health Care; D010865:Pilot Projects; D055815:Young Adult
chemical_list: D016166:Free Radical Scavengers; D007166:Immunosuppressive Agents; D000068717:Glatiramer Acetate; D005978:Glutathione; D000111:Acetylcysteine