Safety and changes in plasma and cerebrospinal fluid amyloid β after a single administration of an amyloid β monoclonal antibody in subjects with Alzheimer disease

Eric R. Siemers, Stuart Friedrich, Robert A. Dean, Celedon R. Gonzales, Martin R. Farlow, Steven M. Paul, Ronald B. Demattos

Research output: Contribution to journalArticlepeer-review

156 Scopus citations

Abstract

Objectives: 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 β (Aβ) 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) Aβ was demonstrated in plasma; CSF total Aβ 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 Aβ was observed, although changes in cognitive scores were not noted. Further studies of solanezumab for the treatment of AD are warranted.

Original languageEnglish (US)
Pages (from-to)67-73
Number of pages7
JournalClinical neuropharmacology
Volume33
Issue number2
DOIs
StatePublished - Mar 1 2010

Keywords

  • Alzheimer disease
  • Amyloid A
  • Immunotherapy
  • Solanezumab

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology
  • Clinical Neurology

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