Challenge 25 years of consensus! The Alzheimer's vaccine is about to begin Phase III clinical trials, and the company's sword refers to the tau protein Achilles.

For decades, Alzheimer's (AD) research has focused on the increasingly controversial beta-amyloid hypothesis.
scientists in Slovakia have been backwatering from the start in search of a new treatment.
alzheimer's disease has recently been plagued by intense disappointment.
25 years, most scientists have followed the beta-amyloid hypothesis that the key driver behind the disease is the accumulation of beta amyloid plaques in the brain.
billions of dollars to develop treatments aimed at removing these plaques, which it hopes will be enough to treat the disease.
early results are promising, late trials of amyloid-targeted drugs by giants such as Yanjian, Merck, Lilly, Pfizer and Roche have been frustrating failures.
the same time, some researchers are looking at another target, the tau protein.
normally, tau protein plays a variety of important roles in the brain, including stabilizing the microcontrove of neurons.
, however, in the brains of AD patients, tau proteins aggregate and form "nerve fiber tangles", which are considered an important marker of the disease.
Slovak-based biotech company Axon Neuroscience focuses on the study of tau proteins.
, the company's founder, has been studying the molecule since the 1980s.
Axon's chief scientific officer, said: "Novak was involved in the initial study of the effects of tau protein on AD development at the MRC Molecular Biology Laboratory in Cambridge, UK.
suggested structural differences in the pathological morphology of tau proteins in the brains of AD patients, which were not found in healthy brains.
no one believed him at the time because there was no available information about the structure of these proteins.
, as early as 1991, studies have suggested that tau protein aggregates are the main driver of AD cognitive decline.
, according to Zilka, a growing body of data suggests that amyloid beta aggregates may be a factor, but not a cause, that affects the rate of cognitive decline.
, the general consensus remains that the beta amyloid hypothesis is adhered to.
15 or 20 years ago, it was difficult to publish some interesting data on tau proteins in the most prestigious scientific journals because they generally tended to be based on beta amyloid, " he explains.
for many really big companies, there are so many bets on the beta amyloid hypothesis that they have to keep going.
Axon's primary goal was to prove whether tau proteins actually underlying the AD brain, so they conducted a very extensive proteomic analysis of tau proteins in the brains of healthy subjects and AD patients.
found significant differences in tau proteins between the two experimental groups.
in individuals with AD, the tau protein loses its natural elastic structure, creating a stronger structure that forms polymers that lead to entanglement of nerve fibers observed in the patient's brain.
the Achilles heel of the tau protein, "We think the most important target is not the tau protein itself, but a small area of the protein."
this area is where tau proteins interact to form aggregates.
," Zilka said.
Axon's team developed an antibody that targets this region to block interactions between tau proteins.
based on the findings, the company began developing a vaccine designed to train the immune system to attack specific areas of the tau protein.
vaccine is designed to be given once a month under the skin for 6 months, followed by every 3 months, so that antibody levels remain high over a longer period of time.
2013, Axon began its first clinical trial in 30 patients with mild to moderate AD.
results show that the vaccine is safe and patients are well-to-do with it.
, the trial showed that the subjects had a very high immune response to the tau protein.
antibodies produced by vaccines can attack harmful tau protein aggregates without affecting their health? It turns out that the pathological form of the tau protein exposes the specific regions that cause it to gather, but in healthy forms, this small area of the protein is hidden.
, Axon completed another Phase II trial of mild AD patients in eight European countries.
they tested the vaccine on 196 patients, who observed very high antibody responses even though they were mostly over 55 years old.
"From other vaccination studies, it is a challenge to induce a strong antibody response in older adults," he said.
, we also observed very high immune responses in 85-year-old patients.
addition, we have determined the effects of the vaccine on several AD biomarkers and clinical outcome measurements, so we have very strong evidence that the vaccine can slow neurodegeneration.
," Zilka said.
Axon is now preparing to begin Phase III clinical trials and, if successful, the vaccine is expected to be available.
tau protein has become "hot" in recent years, in part because of a large-scale autopsy study of more than 3,600 brains published in 2015 by the Mayo Medical Center.
study found that the pathological form of tau protein, rather than beta amyloid protein, was a key driver of AD.
as the beta amyloid hypothesis became more and more challenging, many participants in the AD field began to turn to tau protein as a target.
their main method is to develop monoclonal antibodies that are resistant to tau proteins.
the past six years or so, many large pharmaceutical companies have started to study tau proteins," said Zillka, a pharmaceutical researcher.
I estimate that there are now about 10 different anti-tau protein antibodies in clinical trials.
" 25 years later, Axon's situation has changed.
Zillka believes the company's vaccines will have key advantages over antibody drugs, including lower production costs and easier administration.
, however, with so many devastating and dramatic failures in past research and development, it is harder than ever to convince the industry that any new approach, no matter how promising, will work.
more questions now, especially when we're talking about clinical trials," said Zillka, a research group.
a little cautious about big pharmaceutical companies, they're asking for more and more data.
, we now need more evidence to convince people that we're on the right track than we were in clinical trials 10 or 15 years ago.
" Of course, amyloid and tau proteins are not the only hypothetics.
the mysterious nature of the brain means that many of the factors associated with neurodegenerative changes are still not clear.
many other factors (such as nerve infections, nerve inflammation, oxidative stress, etc.) are thought to be potential causes of the disease.
: "At least 50 percent of the lectures at this year's major AD conferences are about tau protein, " says Zillka.
protein hypothesis is currently at the forefront of AD research.
" Reference: 1 s An Alzheimer's Vaccine Challenged the Consensus for 25 Years (Source: LABIOTECH.eu) 2 s.AADvac1AD Phase II Study (Source: Axon Neuroscience) Scan code for more exciting article copyright and disclaimer White Dew Source: Pharmaceutical Rubik's Cube !-- Content Presentation Ends - !-- To Determine If Login Ends.