The scope and limitations of in vivo and in silico models of cardiac amyloidosis

Amyloidosis is systemic diseases, leading into disfunction of many organs.

There are several clinical and morphological forms of amyloidosis based on the organ-specific nature of the amyloid fibrils deposition, which are found in the heart, brain, kidneys, spleen, liver, pancreas and thyroid glands, bone marrow, intestines. The nature of organ damage correlates with the types of amyloid fibrils. Thus, damage to the tissues of the heart and kidneys are the most significant factors affecting mortality.

The complexity of drug molecules discovery against amyloidosis is connected with the fact the more than 30 proteins are involved in the fibril formation.

The crucial approach for the discovery of drug molecules against cardiac amyloidosis needs the predictive models. The restriction of most developed models connects with their reproducibility and cost. Therefore, in silico approach may be quite effective procedure to minimize time and difficulties during drug discovery process.

In this paper we collected main knowledge which highlights scope and limitations considered during in silico approach development. For this the publications including patents covered past 20 years have been analyzed.

This research was funded by the Russian Science Foundation, project number 21-74-20093. Link to information about the project: https://rscf.ru/en/project/21-74-20093/