Phase 2 results presented this week at the International Conference on Alzheimer's Disease (ICAD) 2008 in Chicago show that a monoclonal antibody to amyloid beta (A-beta) caused no adverse effects, and biomarker evidence suggested the treatment may have efficacy.
"This provides indirect evidence that (the antibody) has an effect on plaque formation, which in theory would slow or prevent progression of Alzheimer's disease," principal investigator Dr. Eric R. Siemers of Eli Lilly and Company in Indianapolis, Indiana, reported.
The monoclonal antibody has been given the investigational name LY2062430. Dr. Siemers and colleagues studied 52 patients with mild-to-moderate AD and 16 healthy volunteers. Patients received 12 weekly infusions of placebo or one of four dosages of the antibody: 100 mg every four weeks, 100 mg once a week, 400 mg every four weeks or 400 mg once a week. Controls received a single 100 mg dose of antibody.
Safety assessments were made, including magnetic resonance imaging studies, to look for evidence of vasogenic edema or hemorrhage in the brain. Plasma and cerebrospinal fluid levels of A-beta concentrations were measured.
Baseline mini-mental status examination (MMSE) score in the AD patients was 20, which did not change significantly during the phase 2 study.
"There were no adverse events of any kind" associated with the antibody, Dr. Siemers told Reuters Health.
Antibody infusion increased total (bound plus unbound) plasma A-beta-1-40 and A-beta-1-42 in a dose-dependent manner, Dr. Siemers reported.
In patients taking 400 mg once a week, antibody treatment decreased unbound CSF A-beta-1-40, while unbound CSF A-beta-1-42 increased in a dose-dependent manner.
For patients treated with 400 mg, baseline iodo-2-(4-dimethylamino-)phenyl-imidazo(1,2-a)pyridine (IMPY) signal in the cingulate cortex correlated with plasma A-beta 1-42 concentrations seven days after the first infusion.
Antibody produced no measurable change in cognition scores or IMPY scans, "but we didn't expect to find any changes in cognitive status in a 12-week study," Dr. Siemers said.
"We think the antibody binds to amyloid beta protein. We don't think it binds directly to plaque, but only to soluble monomers. It has an indirect effect on plaque formation by inhibiting A-beta protein. This increased clearance of A-beta prevents plaque formation," Dr. Siemers explained.
