Immunotherapy with the antibody bapineuzumab in patients with mild to moderate Alzheimer’s disease (AD) resulted in decreases in a cerebrospinal fluid biomarker, which may indicate downstream effects on the degenerative process, according to Phase II research published online April 2 in the Archives of Neurology.
AD is a progressive neurodegenerative disease characterized by, among other things, deposits of extracellular B-amyloid (AB) plaques and intraneuronal neurofibrillary tangles with accompanying decreases in cerebrospinal fluid (CSF) AB and increases in CSF tau proteins, the study authors wrote. Bapineuzumab is an anti-AB monoclonal antibody, and immunotherapy with antibodies against AB is one of the major disease-modifying therapeutic approaches being evaluated for AD. The researchers noted that the pharmacokinetic characteristics of bapineuzumab include a small distribution volume, slow clearance and long terminal half-life.
Kaj Blennow, MD, PhD, adjunctive professor of neurology and epilepsy at the University of Gothenburg in Gothenburg, Sweden, and colleagues conducted a combined analysis of two double-blind, placebo-controlled trials that included 46 patients with mild to moderate AD.
The researchers enrolled a total of 27 patients; eight were treated with bapineuzumab and 19 with placebo. They evaluated whether bapineuzumab affected the CSF levels of the downstream biomarkers, total tau (T-tau) and phosphorylated tau (P-tau), as well as the primary biomarker AB in the completed trials.
One limitation of study, according to the study authors, is that it is based on pooled analysis of the bapineuzumab trials Study 201 and Study 202, which was done to increase the sample size of patients in each sub-study with paired CSF samples. “However, for both trials, CSF biomarkers were analyzed in the same laboratory using the same assay formats, CSF samples from individual cases were analyzed side by side on the same ELISA plate and data were analyzed as the change in biomarker levels between baseline and end of study,” they wrote. “This procedure will minimize variation and allow pooling of CSF data.
“The reduction in the downstream biomarker CSF P-tau following treatment with bapineuzumab suggests that bapineuzumab reduces brain levels of P-tau, which may also reduce the formation of tangles in the brain,” the study authors wrote.
Although there was a reduction in CSF T-tau, Blennow and colleagues noted that it did not reach statistical significance compared with placebo. The study results indicated no clear-cut differences were observed for CSF AB.
However, they noted that the observed decrease in both P-tau and T-tau require further examination.
“An important question remains whether such changes in CSF biomarkers correlate with clinical benefit. This question will be addressed in the ongoing bapineuzumab Phase III trials,” the authors concluded.