title: Safety and changes in plasma and cerebrospinal fluid amyloid beta after a single administration of an amyloid beta monoclonal antibody in subjects with Alzheimer disease.
abstract: OBJECTIVE
  Active and passive immunization strategies have been suggested as possible options for the treatment of Alzheimer disease (AD). LY2062430 (solanezumab) is a humanized monoclonal antibody being studied as a putative disease-modifying treatment of AD.
  
  
  METHODS
  Patients with mild to moderate AD were screened and selected for inclusion. Initial screening was performed for 54 subjects, and 29 of these underwent additional screening; after this second screening, a total of 19 subjects were included. Single doses of solanezumab using 0.5, 1.5, 4.0, and 10.0 mg/kg were administered. Safety assessments included gadolinium-enhanced magnetic resonance imaging of the brain and cerebrospinal fluid (CSF) analyses at baseline and 21 days after dosing. Plasma and CSF concentrations of solanezumab and amyloid beta (Abeta) and cognitive evaluations were obtained.
  
  
  RESULTS
  Administration of solanezumab was generally well tolerated except that mild self-limited symptoms consistent with infusion reactions occurred for 2 of 4 subjects given 10 mg/kg. No evidence of meningoencephalitis, microhemorrhage, or vasogenic edema was present based on magnetic resonance image and CSF analyses. A substantial dose-dependent increase in total (bound plus unbound) Abeta was demonstrated in plasma; CSF total Abeta also increased. No changes in cognitive scores occurred.
  
  
  CONCLUSIONS
  A single dose of solanezumab was generally well tolerated, although infusion reactions similar to those seen with administration of other proteins may occur with higher doses. A dose-dependent change in plasma and CSF Abeta was observed, although changes in cognitive scores were not noted. Further studies of solanezumab for the treatment of AD are warranted.
authors.affiliation: Eli Lilly and Company, Lilly Research Laboratories, Indianapolis, Indiana 46285, USA. esiemers@lilly.com
authors.forename: Eric R
authors.initials: ER
authors.lastname: Siemers
authors.forename: Stuart
authors.initials: S
authors.lastname: Friedrich
authors.forename: Robert A
authors.initials: RA
authors.lastname: Dean
authors.forename: Celedon R
authors.initials: CR
authors.lastname: Gonzales
authors.forename: Martin R
authors.initials: MR
authors.lastname: Farlow
authors.forename: Steven M
authors.initials: SM
authors.lastname: Paul
authors.forename: Ronald B
authors.initials: RB
authors.lastname: Demattos
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000097:blood / Q000134:cerebrospinal fluid / Q000188:drug therapy*; D016229:Amyloid beta-Peptides / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D003071:Cognition / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos
chemical_list: D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D010919:Placebos; C550616:solanezumab