Biomedicine & Pharmacotherapy

Biography

Biography: Sergey Suchkov

Abstract

New therapies for autoimmune and inflammatory diseases require greater understanding of patient or persons-at-risk subsets and the ability to personalize targeted therapies. In this sense, the identification and application of diagnostic, predictive and prognostic biomarkers remains the holy grail of PM-related platforms, algorithms and protocols. Among the best-validated predictive biomarkers are autoimmunity-related ones to predict risks of the chronification and thus disabling. Abs against myelin basic protein/MBP with proteolytic activity exhibiting sequence-specific cleavage of MBP is of great value to monitor demyelination whilst in MS. The activity of Ab-proteases was first registered at the subclinical stages 1-2 years prior to the clinical illness and revealed significant correlation with scales of demyelination and the disability of the patients as well. Canonical auto-Abs play neither predictive nor discriminative role to affect the subclinical stage of MS. Meanwhile, Ab-proteases have proved to be greatly informative and thus valuable as biomarkers to monitor MS at both subclinical and clinical stages! So, the activity of Ab-proteases and its dynamics tested would confirm a high subclinical and predictive (translational) value of the tools as applicable for personalized monitoring protocols at both subclinical and clinical stages of the disorder. Therefore, the proposed predictive value of MBP-targeted Ab-proteases for the development of MS is being challenged. In this sense, Ab-proteases can be programmed and re-programmed to suit the needs of the body metabolism or could be designed for the development of principally new catalysts with no natural counterparts. By changing sequence specificity one may reach reduction of a density of the negative proteolytic effects within the myelin sheath and thus minimizing scales of demyelination. Targeted Ab-mediated proteolysis could be also applied to isolate from Ig molecules catalytic domains directed against encephalitogenic autoepitopes or domains containing segments to exert proteolytic activity. Further studies are needed to secure artificial or edited Ab-proteases as translational tools of the newest generation to diagnose, to monitor, to control and to treat and rehabilitate MS patients at clinical stages and to prevent the disorder at subclinical stages in persons-at-risks to secure the efficacy of regenerative manipulations.