Antisense oligonucleotides against tau protein
The synthesis of pathological protein in Alzheimer's disease can be stopped
Anna Stavina, XX2 century, based on ScienceDaily: Designer compound may untangle damage leading to some dementias
The process of brain damage caused by exposure to a toxic variety of tau protein can not only be stopped, but also reversed to a certain extent. To do this, as reported in the new study, it is necessary to use specific antisense oligonucleotides that block the synthesis of tau protein in cells. Theoretically, these compounds could be used in the treatment of various neurodegenerative diseases.
Normally, the cells of the human body synthesize tau protein. It participates in the stabilization of microtubules, organoids that form the cellular "skeleton". However, in some diseases, pathological modification of tau protein forms neurofibrillary tangles inside brain cells.
This occurs, in particular, in Alzheimer's disease, frontotemporal dementia, chronic traumatic encephalopathy and progressive supranuclear paralysis. Currently, there are no means that can reduce the harm from exposure to a toxic variety of tau protein.
Antisense oligonucleotides are short sequences of DNA or RNA designed to "turn on" or "turn off" genes. The senior author of the work, Dr. Timothy Miller, professor of neurology at Washington University in St. Louis, explained that these compounds can literally "unravel" the tangles of tau protein and reduce the harm they cause.
Antisense therapy is a treatment method based on switching off/stopping the synthesis of a protein involved in the development of the disease by inhibiting the translation of its matrix RNA using short nucleotide sequences complementary to it (antisense oligonucleotides).
Antisense oligonucleotides are used in oncology to suppress the synthesis of tumor proteins. In addition, the US Food and Drug Administration has recently approved the use of the drug Nusinersen (Nusinersen) based on antisense oligonucleotides for the treatment of spinal muscular atrophy (SMA), a hereditary disease that leads to weakening of the muscles of the body and often to death due to paralysis of the respiratory muscles. Earlier we have already written about the promising results of trials of this drug.
Researchers led by Sarah DeVos, a graduate student from Professor Miller's laboratory, tested the specific antisense oligonucleotides they developed on mice. The animals were previously genetically modified in such a way that pathological forms of tau protein were produced in large quantities in their bodies. Neurofibrillary tangles in the brain of such mice began to form when the animals reached the age of 6 months. Neurological symptoms also appeared at the same time. The mice genetically modified in this way died earlier than the animals from the control group.
The introduction of oligonucleotides into the fluid surrounding the brain of mice was able to prevent the appearance of neurofibrillary tangles in mice aged 6 to 9 months. If injections were given to older animals, the tangles partially disappeared. Such mice lived longer than placebo-treated animals and also retained the ability to build nests, usually lost with age.
Further experiments on primates demonstrated that antisense oligonucleotides can penetrate into diseased areas of the brain, which is significantly larger than a mouse brain. At the same time, the effectiveness of treatment was maintained. And, as experiments on mice have shown, oligonucleotide therapy is well tolerated and practically does not cause side effects.
However, for the introduction of a new drug into medical practice, additional tests of its effectiveness and safety will be required. Currently, researchers are engaged in conducting early clinical trials of antisense oligonucleotides intended for the treatment of Huntington's disease and amyotrophic lateral sclerosis.
Article by Morton et al. Abnormal neurogenesis and cortical growth in congenital heart disease is published in the journal Science Translational Medicine.
Portal "Eternal youth" http://vechnayamolodost.ru 09.02.2017