Alzheimer's is one of the most widespread diseases in elderly people.
People over the age of 60 are at the greatest risk of developing the
disease, but it can also occur at a younger age.
Patients suffer from
loss of memory and cognitive functions; they become socially detached
and lose their independence, and the body can no longer function
properly, which inevitably leads to death.
‘Molecules that could potentially treat Alzheimer's disease have been discovered by researchers.’
According to medical
statistics, Alzheimer's is the cause of two out of every three cases of
dementia in the elderly and it is a huge economic problem in developed
countries - the financial impact in the US, for example, is higher than
for cancer or cardiovascular diseases.
Scientists have not yet succeeded in finding an effective cure for
Alzheimer's. Despite the fact that we know how the disease develops, we
cannot say that we are even close to a solution. Pharmaceutical studies
are still being conducted in order to be able to reduce the symptoms of
This year, results have been published of two significant research
studies about molecules that could potentially treat Alzheimer's
disease. The chief researcher in both studies was the head of the
Laboratory of Medical Chemistry and Bioinformatics at MIPT Yan
Ivanenkov. Papers on the two new molecules were published in Molecular Pharmaceutics and Current Alzheimer Research
. Mark Veselov, another MIPT employee, also participated in the second study.
Both papers cover the study of neuroprotectors - antagonists to the
5-HT6R receptor. The latest research confirms that this target has a
high therapeutic potential in the treatment of Alzheimer's disease.
Preclinical studies on lab animals have shown that the compounds have a
In the first paper, specialists Alexander Ivashenko and Yan Lavrovsky
from Alla Chem LLC, Avineuro Pharmaceuticals Inc. and R-Pharm Overseas
Inc. (all US companies), in collaboration with MIPT's Yan Ivanenkov,
worked on a 5-HT6R activity blocking compound. A similar task was
investigated in Yan and Alexander's second study with another MIPT
employee, Mark Veselov.
5-HT6R receptors were chosen because they are
integrated into nerve cell membranes and are capable of reacting to
certain external signals, which is why scientists consider them as
targets for AD treatment. The antagonists to the receptor are able to
ease the symptoms of the disease in a clinical environment.
Scientists studied the pharmacokinetic features, activity,
efficiency, and also the toxicity profile of AVN-211. First, a screening
test was performed using recombinant human cells containing 5-HT6R to
make sure that AVN-211 really is an antagonist. Another series of
experiments with cell cultures demonstrated its ability to spread in a
tissue and provided preliminary data about its state in the human body -
metabolism, biochemical interactions, etc.
Tests were then performed on lab animals - mice, rats and monkeys to
obtain the pharmacokinetic profile of a drug candidate in a real body.
Observing concentration changes in the animals' blood after intake
provided information about the compound's pharmacodynamics.
Memory disorder stress tests have shown that AVN-211 might be able to
improve memory function. Rats and mice were taught to find an exit from
a maze, while their cognition was imaired by drugs provoking memory
loss. Animals who were given the drug demonstrated better results. In
addition, healthy animals who received the new drug were better learners
and could be trained more efficiently.
These results led the researchers to believe that AVN-211 will be able to combat cognitive dysfunction caused by AD.
Scientists also think that this compound can be used to treat certain
mental disorders. Tests with chemicals that produce the same symptoms
as psychosis have shown a possible antipsychotic and anxiolytic
(reducing anxiety) effect. Such effects are used in treating
schizophrenia and depression. It was also noticed that AVN has a
comparable effect to haloperidol - a common antipsychotic drug.
In vitro studies revealed that this compound affects the 5-HT6R
receptor more effectively and selectively compared to all other drugs,
including those currently in clinical trials. Studies on lab animals
showed that AVN-211 has low toxicity.
The same tests were performed for AVN-322. Screening with the 5-HT6R
receptor on human cell culture proved that the molecule is a highly
effective antagonist. In vivo tests were performed on mice: the animals
were taught how to get out of a maze and had to remember that a section
of the floor was electrified. The results showed that mice that received
low levels of AVN-322 performed better than after any existing
The pharmacokinetics of AVN-322 were analyzed in mice, rats, dogs and
monkeys. During a 30-day intake monkeys did not have any toxic
after-effects. A possible danger was noticed after a 180-day intake in
rats - the substance can cause brachycardia and hypotension. However the
exact after-effects are less serious than all other existing drugs.
Pre-clinical data proves that AVN-322 also has a good pharmacokinetic
profile - it is very digestible and passes well through the blood-brain
In conclusion, we can say that both compounds have a high
pharmaceutical potential and low toxicity. The positive results of the
studies mean that researchers can move on to clinical trials in order to
verify the safety and effectiveness of a drug that could potentially
treat one of the most serious diseases of our time.