Antibodies to repair the brain

The cure for many diseases will be rare antibodies

Yulia Vorobyova, Vesti

Not so long ago, researchers proved that Alzheimer's and Parkinson's diseases, despite all the difference between them, begin and develop the same way at the biochemical level. We are talking about sticky proteins that form plaques in brain tissues.

This discovery significantly accelerated the development of tools for the treatment and prevention of neurodegenerative diseases. So, scientists from the New York University School of Medicine have proposed their own approach - therapy using antibodies that separate proteins and prevent them from sticking together.

Let's explain that in Alzheimer's disease, the "destroyers" are tau proteins that form neurofibrillary tangles. In Parkinson's disease, the sticky protein is alpha-synuclein, which forms Levi's corpuscles. Moreover, there is another neurodegenerative disease that develops according to the same principle – this is "mad cow disease", which is provoked by prion proteins.

For more than a decade, researchers have been studying the brain tissues of patients with these diseases, which became available after autopsy. They also examined the course of diseases using the example of laboratory rodents. Experiments have shown that special antibodies acting selectively and having no immune toxicity will help prevent the formation of protein plaques.

The leading authors of the work, Fernando Goni and Thomas Wisniewski, admit that this approach may contradict traditional methods, and they still have to conduct a number of studies before clinical trials.

Nevertheless, the current results are encouraging. "Antibodies can stop key pathological processes occurring in several neurological diseases, regardless of their stage," says Vishnevsky.

To understand how diseases originate at the molecular level, experts focused on the process of forming the building and working material of cells – proteins. While they are formed in the form of chains of amino acids, they also add up to complex bulk structures. The way the parts of the protein molecule are oriented relative to each other affects their performance. That is, the protein can be "broken", which means that it provokes the disease not only in terms of composition, but also structure.

Factors such as toxins, genetic "breakdowns", inflammatory processes or age-related changes at the cellular level can cause the protein to "fold" incorrectly and then begin to perform its functions incorrectly.

Many research groups have tried to use antibody therapy, but the latter were either aimed at repeating short chains of amino acids that make up a large molecule of an improperly formed protein, or at final plaques consisting of thousands of monomers, it is almost impossible to understand the intricacies of which.

Goni and Vishnevsky took a different approach: they forced antibodies to attack oligomers – "bricks" of proteins larger than monomers, but smaller than the protein molecules themselves. According to the authors, such intermediate forms are toxic and dangerous in their own way even more than others, since they are mobile. They can dissolve, move inside and outside of cells, as well as "move" from one cell to another.

The researchers note an important detail: in the growing toxic oligomers, which will later form alpha-, beta- and tau-synuclein, as well as prions, there are a large number of special structures – beta sheets.

As for the "rescue" antibodies themselves, an extremely rare disease, amyloidosis, helped scientists in their creation. This is a genetic disease in which protein metabolism is disrupted, and this is accompanied by the formation and deposition in the tissues of a specific protein-polysaccharide complex – amyloid. The disease has several forms, among which there is "British amyloidosis" (as the name implies, it does not occur in residents of other countries).

The specialists worked with the same amyloid – a peptide of 13 amino acids. It was turned into a larger stable oligomer, which repeats the shape of the beta sheet with 90% accuracy. So scientists have created an immunogen (an antigen that causes an immune response) called p13Bri. Experiments with mice have shown that p13Bri provokes a specific immune response in their body: rare antibodies that destroy beta sheets begin to be produced.

The team tested their development using the tissues of people who had suffered from Alzheimer's, Parkinson's and neurological diseases caused by prions. In all cases, the effect was positive.

Moreover, according to the authors, these rare antibodies activated by amyloid have almost zero chance of triggering unwanted immune responses and attacking beneficial proteins.

Although there is still a lot of work to be done, scientists are confident that they are on the right track. Goni and Vishnevsky, together with colleagues, will continue to develop a unified method of therapy, with which, they hope, it will be possible to treat a huge range of neurological diseases.

The team describes its research in detail in the publication Scientific Reports.

Portal "Eternal youth" http://vechnayamolodost.ru  01.09.2017