Create database of amyloid plaque inhibitors that cause Alzheimer’s disease.

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Create database of amyloid plaque inhibitors that cause Alzheimer’s disease. To date, none of the phase III clinical trials aimed at anti-AD therapy have demonstrated a statistically significant treatment effect in patients with AD.

We have proposed a completely new principle of blocking the formation of amyloid plaques in terms of the stability of the biological complex. We will increase the stability of amyloid peptides at the level of dimeric low molecular weight complexes.

Alzheimer’s disease (AD) is the most common form of dementia that affects everyday life through memory loss and cognitive changes. The Alzheimer’s Association reports that one in ten people over 65 and almost one third of people over 85 have Alzheimer’s disease.
Symptoms of Alzheimer’s disease usually develop slowly with a tendency to gradually worsen over time, moving from mild forgetfulness to widespread brain disorders. To date, none of the phase III clinical trials aimed at anti-AD therapy have demonstrated a statistically significant treatment effect in patients with AD. Therapeutic approaches included the use of monoclonal antibodies that recognize different Aβ epitopes and exhibit different binding selectivity [Clinical Development of Aducanumab, an Anti-Aβ Human Monoclonal Antibody Being Investigated for the Treatment of Early Alzheimer’s Disease.]

Based on the developed concept, we propose a method of inhibiting amyloid peptides. The concept was based on data on the characteristics of the formation of high molecular weight structural amyloid peptides.

For the first time, a new method was proposed that explains the formation of high-molecular-weight amyloid structures from the point of view of the stability of amyloid complexes.

A numerical gradation was given for a three-dimensional structure from a PDB base according to the degree of stability of amyloid dimers. A value was introduced with a value equal to 5.33, which determines the stability of the biocomplex. At the same time, she conditionally divided dimers with reduced and increased propensity to form high molecular weight structures. The value 5.53 was found on the basis of a comparison with experimental data on mutations in amyloid peptides, their physiological and biophysical characteristics, and the ability to appear in all new biochemical reactions.


 In this part, we will examine in detail the biophysical requirements for inhibitors, the criteria and conditions for their selection. We consider modified peptides that will form stable dimers with amyloid peptides, thereby preventing the entry of amyloids into all new biochemical reactions.

The beta amyloid peptid consists of about 30 amino acids. It aggregates to amyloid plaques, that may damage and kill neurons by generating reactive oxygen species during it self-aggregation.

The figure shows the amino acid sequence of the amyloid peptide AB(11-42) indicating previously identified mutations, each of which is characterized by its physiological effect on the human body due to various biochemical aspects due to the various interactions of amyloid peptides.

Let us consider more detailed some of the previously proposed drugs for the treatment of AD. Adukanumab is a high-affinity fully human monoclonal IgG1 monoclonal antibody against the conformational Aβ epitope. It was originally obtained by the biotechnology company Neurimmune in Schlieren, Switzerland, from healthy elderly donors who were cognitively healthy. The rationale was that the immune system of these donors successfully resisted Alzheimer’s disease and that antibodies could be converted into therapeutic agents.
Side effects of aducanumab include headache, diarrhea, and dizziness.
On April 24, 2019, Biogen announced that it would not initiate the anticipated phase III program with aducanumab and removed it from its assembly line.

{There is currently conflicting news about the drug adukanumab, in particular, the issue of its effectiveness and possible approval by FDA is being addressed.}

Gantenerumab is another fully human IgG1 antibody designed to bind to a subnanomolar affinity for a conformational epitope on Aβ fibrils. It covers both the N-terminal and central amino acids of Aβ. On December 19, 2014, Roche discontinued the study based on an interim utility analysis.

Basic requirements for amyloid peptide inhibitors

Inhibitors should be characterized by the following parameters:

  • formation of a stable dimer with the amyloid peptide of the wild form [wtAβ + IngAB] if it is desired to inhibit the peptide of the wild form or formation of a stable dimer with the mutant form of the amyloid peptide [mutAβ + IngAB] if it is required to inhibit the amyloid of the mutant form. The range of lg (cond (w)) should be in the range below 5.53 (in the case of using the three-dimensional PDB structure: 4MUI)
  • the formation of a stable dimeric complex upon reaction with the same inhibitor [inhAβ + IngAB]. The range of stability values ​​during the interaction of two identical inhibitors with each other should be in the range of values ​​below 5.53 (in the case of using the three-dimensional structure of PDB: 4MUI)

We selected a three-dimensional structure from the PDB database: 4MUI, calculated for them the potential energy of electrostatic pairwise interaction between the amino acid residues of two neighboring chains, and obtained a matrix of potential energy of electrostatic interaction (data on request).


To significantly reduce all possible variants of possible amino acid substitutions, we used the assumption that a decrease in the peak values ​​of potential energy during the interaction of two polypeptide amino acid sequences can lead to a decrease in the entropy of the biological complex, which in turn can indicate a transition of the biological complex to a more ordered state. In this case, we will control the dimer stability value by the criterion lg (cond (w)) introduced by us earlier.

Alzheimer’s donation

RISCS and conditions:

We are a successful group of developers who created a startup company at an early stage.
The project involves several stages:
1. The first stage — creating a database is associated with a minimum level of risk, except for such as force majeure circumstances are possible such as the loss of working ability by one of the developers, natural, economic and political disasters. In case of insufficient funding, the deadlines may increase; if there is a lack of financing, this is not a condition for canceling the project
2. The second stage contains the experimental verification of selectively found immunoglobulins in vitro.
At this stage, additional time may be required to adjust and debug the selection of immunoglobulins. Our method is in good agreement with in vitro experts, however, we cannot guarantee the successful completion of experiments in vivo, on cell lines, of small animals.
3. Search for partners and patenting developed molecules

Patenting is not common for countries all over the world and is actually unique for each individual country. Also, maintaining a patent is an expensive labor-intensive process, therefore we cannot guarantee successful completion of the project starting from the third paragraph, since in this case third parties enter the game.Pre-clinical studies, determination of the best candidates, selection of the best molecules. We cannot give a 100% guarantee for cases in vivo. Also, we cannot guarantee a successful search for partners to work on conditions that suit all parties.

4.Clinical studies. We can only switch to clinical trials after successfully completing all preclinical trials.

5.Wide coverage of work results in publications, at conferences, startup presentation

6.Conclusion of contracts for the transfer of patents to research laboratories, pharmacological companies.

7.Fulfillment of orders to third parties

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