Scientists have reported that their vaccine called AADvac1, designed to target a pathological form of the protein Tau in the brain, was well tolerated and able to elicit immune responses in people with mild Alzheimer's disease. Further studies are needed to determine its effect on cognitive decline in all patients.
Thanks to vaccinations, several diseases have been eliminated or controlled. Although we think mainly of diseases whose infectious agent is a virus or a bacterium, this is not the only case. Researchers at the biotechnology company Axon Neuroscience have announced that an experimental vaccine designed to protect against Alzheimer's disease has passed the final stage of human clinical trials. In a Phase II trial, the drug candidate AADvac1 proved to be well tolerated by patients and produced a response against certain markers of the disease, notably the protein tau, whose accumulation in abnormal form is incriminated in many dementias.
In Alzheimer's disease, two pathological phenomena are well described: the accumulation of beta-amyloid peptides and the transformation of the tau protein into abnormally aggregated forms. As Inserm explains, together they progressively promote neuronal degeneration, loss of memory and executive functions. "Although amyloid influences the rate of progression of Alzheimer's disease, there is evidence that tau pathology is linked to the underlying cause of the disease. ", explains Dr. Petr Novak. "Brain atrophy and cognitive loss closely echo pathological tau protein deposition. "
About 10 injections over several months
The 24-month clinical trial involved 196 people with a clinical diagnosis of Alzheimer's disease, of whom 117 became members of the vaccine group and 79 members of the placebo group. About 17% of participants withdrew during the study period, leaving 100 people in the vaccine group and 63 in the placebo group. The vaccine was administered at 40 µg per dose: six monthly subcutaneous injections, followed by five quarterly booster injections. The results showed that the patients showed high levels of immunoglobulin G (IgG) antibodies. In the order of 96.5% at the end of the first six doses and 98.3% overall.
Specifically, the vaccine promotes the production of antibodies that attack floating tau proteins before they form "tangles" that clog neurons and damage brain function. Six patients treated with AADvac1 experienced confusion, mostly transient. "Because confusion occurs naturally in patients with Alzheimer's disease, a larger study is needed to assess whether this is an adverse effect or an incidental finding. Currently, this is a potential risk of moderate significance. "This is a potential risk of moderate importance," said Axon Neuroscience, which published its findings in the scientific journal Nature Aging.
Cognitive decline slowed in a small group of patients with a specific profile
In a subgroup of 109 participants most likely to have Alzheimer's disease because they were most likely to have an abnormal accumulation of tau proteins based on medical test results, assessments of their rate of dementia and activities of daily living suggested that the vaccine was able to slow their cognitive and functional decline by up to 30% compared to the placebo group. "This is the first time that a targeted tau immunotherapy has shown clear evidence of impact on the neurodegenerative process and a strong indication of clinical effect in patients with a confirmed biomarker profile of Alzheimer's disease," added Dr. Petr Novak.
The vaccine, which is based on the principle of "immunotherapy," does have its limitations, however, since while it reduces the level of toxic tau proteins in the brain, it did not slow cognitive decline in all patients. But the company notes that these results come from a small, early Phase II clinical trial designed primarily to test its safety. So it plans to conduct a Phase IIb study in patients whose tests show that Alzheimer's disease is specifically linked to biomarkers suggesting that tau protein is responsible for their dementia. The study is expected to be launched in a larger sample of patients early next year.
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