CHICAGO — An investigational monoclonal antibody may dissolve amyloid brain plaques in patients with Alzheimer's, though patients receiving it had no signs of improved cognition.
Dr. Eric Siemers, who presented the data from the trial, sponsored by Eli Lilly & Co., at the International Conference on Alzheimer's Disease, said the lack of cognitive improvements didn't trouble him. The 12-week period was probably too short to show any cognitive changes, said Dr. Siemers, medical director of Lilly's Alzheimer's Disease Research Team.
The vaccine (LY2062430) was safe for the Alzheimer's patients and healthy volunteers who received it, Dr. Siemers said. There were no infusion reactions or drug-related adverse events.
The study comprised 52 patients with mild-moderate Alzheimer's (mean Mini-Mental State Exam score 20) and 16 healthy volunteers. Patients were randomized to placebo or to one of four antibody infusions: 100 mg every 4 weeks, 100 mg every week, 400 mg every 4 weeks, or 400 mg every week. Volunteers got one 100-mg dose.
All patients underwent magnetic resonance imaging and blood and cerebrospinal fluid (CSF) sampling to determine the level of soluble amyloid β. A subgroup of 24 patients and 13 volunteers also underwent single-photon emission computed tomography (SPECT) to determine cortical amyloid plaque load. Cognitive status was assessed by the Alzheimer's Disease Assessment Scale-Cognition (ADAS-cog).
CSF and blood samples showed that the antibody affected levels of both Aβ40 (a less-neurotoxic protein) and Aβ42 (the toxic form in AD brain plaques) in a dose-dependent manner. Patients on the 400-mg/wk dose had a significant decrease in Aβ42 but a significant increase in Aβ42, suggesting the brain plaques were dissolving.
“Additionally, after treatment, we found correlation between β amyloid in the blood and the amount of amyloid plaque in the brain as determined by imaging, as well as the increase in blood and CSF of certain types of β amyloid found in plaques. These biomarker data suggest that the plaques in the brain may begin to dissolve after 12 weeks of treatment.”
A phase III trial will begin in 2009. The meeting was sponsored by the Alzheimer's Association.