The vaccine AADvac1 was found to be both safe and capable of eliciting an immune response in patients with mild Alzheimer’s disease (AD), according to a phase 2 clinical trial published in Nature Aging. However, AADvac1 did not detectably impact cognitive decline in patients.
The accumulation and spread of toxic forms of a protein called tau in the brain of patients with AD is a pathological hallmark of the disease. It is thought to be responsible for the widespread death of neurons that ultimately leads to dementia. Immunotherapy is currently under consideration as a strategy to decrease the levels of toxic tau proteins and help slow cognitive decline in patients.
Petr Novak and colleagues conducted a phase 2, randomized placebo-controlled trial in which they administered several doses of a peptide vaccine called AADvac1, or placebo, to 196 patients (mean age 71.4 years; 45.1% male; 100% white) with mild AD and monitored the vaccine’s safety, immunogenicity — its ability to stimulate an immune response — and clinical efficacy over two years. The authors found that the vaccine was safe and that it led to high levels of antibodies against the vaccine’s peptide in the treated group. However, the vaccine did not lead to statistically significant positive or negative effects on congnition in the whole study sample. Exploratory analyses suggested that AADvac1 slowed the accumulation of plasma neurofilament light-chain protein (NfL) — a marker of neurodegeneration.
The authors conclude that although AADvac1 was well tolerated and led to an immune response against tau, it did not result in statistically significant cognitive benefits, potentially because a number of patients did not have AD tau pathology or of the study’s small sample size. Larger trials stratified according to the presence of disease biomarkers with patients who are therefore needed to replicate these results and adequately test the possible clinical efficacy of AADvac1.
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