Antibody-Proteases as the Upgraded Translational Tools of the Next-Step Generation in Personalized and Precision Neurology Practice to Monitor Multiple Sclerosis at Clinical and Subclinical Stages
Sergey Suchkov1*, Noel Rose2, Aleks Gabibov3 , Harry W. Schroeder4 , Trevor Marshall5 , Abner Notkins6
1Institute for Global Health & Biotech of MGUPP, Russia
2,5Autoimmunity Research Foundation, Los Angeles, CA, USA
3Institute for Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia
4Division of Clinical Immunology and Rheumatology, University of Alabama aBirmingham,UAB,USA
6National Institutes of Health (NIH), Bethesda, MD, USA.
Citation: Suchkov S, Rose N, Gabibov A, Schroeder HW, Marshall T et al (2023) Antibody-Proteases as the Upgraded Translational Tools of the Next-Step Generation in Personalized and Precision Neurology Practice to Monitor Multiple Sclerosis at Clinical and Subclinical Stages. SciTech Neuro-Mental Health 2023.
Received: June 19, 2023 Accepted: June 22, 2023 Published: June 22, 2023
Abstract
Multiple sclerosis (MS) is just one of the chronic tissue-specific autoimmune diseases resulting in a destruction of myelin by different tools, including autoAbs of very broad specificity. Along with canonical Abs, some of the families proven to occur are Abs possessing with catalytic activity (abzymes), and thus to belong to Abs with functionality!
Abs against myelin basic protein/MBP endowing with proteolytic activity (Ab-proteases with functionality) are of great value to monitor demyelination to illustrate the evolution of MS. Anti-MB autoAbs from MS patients and mice with EAE exhibited specific proteolytic cleavage of MBP which, in turn, markedly differed between: (i) MS patients and healthy controls; (ii) different clinical MS courses;(iii) EDSS scales of demyelination to correlate with the disability of MS patients to predict thectransformation prior to changes of the clinical course.
Ab-mediated proteolysis of MBP was shown to be sequence-specific whilst demonstrating five sites of preferential proteolysis to be located within the immunodominant regions of MBP and to fall inside into 5 sequences fixed. Some of the latter (with the highest encephalitogenic properties) were proved to act as a specific inducer of EAE and to be attacked by the MBP-targeted Ab-proteases in MS patients with the most severe (progradient) clinical courses. The other ones whilst being less immunogenic happened to be EAE inducers very rare but were shown to be attacked by Ab-proteases in MS patients with moderate (remission-type) courses.
The activity of Ab-proteases was first registered at the subclinical stages 1-2 years prior to the clinical illness. Sequence-specific Ab-proteases have proved to be greatly informative and thus valuable biomarkers to monitor MS at both subclinical and clinical stages! And the translational potential of this knowledge is in the rational design of new diagnostic tools and new therapeutics based on principles of artificial biocatalysts and Biodesign.
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. Therefore, the proposed predictive value of MBP-targeted Ab-proteases for the development of MS is being challenged! Of tremendous value in this sense are Ab-proteases directly affecting the physiologic remodelling of tissues with multilevel architectonics (for instance, myelin)., whilst securing the requests and standards of regeneration and remyelination.
