Hydrolysis and Dissolution of Amyloids by Catabodies

Methods Mol Biol. 2017;1643:111-134. doi: 10.1007/978-1-4939-7180-0_9.

Abstract

Catalytic antibodies (catabodies) hold potential for superior immunotherapy because of their turnover capability and no or minimal induction of inflammatory responses. Catabodies neutralize and remove target antigens more potently than conventional antibodies. Depending on the catalytic rate constant, a single catabody molecule degrades thousands to millions of target molecules over its useful lifespan, whereas conventional antibodies only form reversibly associated, stoichiometric complexes with the target. Thus, removal of the antibody-bound target requires accessory phagocytic cells that ingest the immune complexes, which is usually accompanied by release of inflammatory mediators. In comparison, catabodies bind the target only transiently, and the rapid and direct target destruction reduces the concentration of immune complexes that can activate inflammatory processes. These features are especially pertinent when large target amounts at anatomically vulnerable sites must be removed, e.g., amyloids. We reported specific catabodies to misfolded transthyretin (misTTR) amyloid and amyloid β peptide (Aβ). Accumulation of the oligomeric and fibrillized amyloid TTR forms causes diverse systemic pathologies, including cardiomyopathy, polyneuropathy, and skeletal diseases. Brain Aβ aggregates are thought to cause central nervous system degenerative disease, chiefly Alzheimer's disease. We describe methods for testing catabody-mediated degradation and dissolution of Aβ and TTR.

Keywords: Amyloid beta; Amyloids; Catalytic antibodies; Dissolution assay; Hydrolysis assay; Transthyretin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / chemistry
  • Amyloid beta-Peptides / immunology*
  • Amyloid beta-Peptides / metabolism*
  • Antibodies, Catalytic / immunology*
  • Antibodies, Catalytic / isolation & purification
  • Antibodies, Catalytic / metabolism*
  • Humans
  • Hydrolysis
  • Immunoglobulin M / immunology
  • Immunoglobulin M / isolation & purification
  • Immunoglobulin M / metabolism
  • Solubility
  • Substrate Specificity

Substances

  • Amyloid beta-Peptides
  • Antibodies, Catalytic
  • Immunoglobulin M