Peptide mapping for analysis of PTMs of innovative reference mAbs for Alzheimer's Disease and biosimilars by CE-MS: verification of the potential of the least expensive drug for therapy.

• Grant number: 24/03238-2
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: August 01, 2024
• End date: August 31, 2028
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Analytical Chemistry
• Principal Investigator: Emanuel Carrilho
• Grantee: Letícia Gaiola
• Host Institution: Instituto de Química de São Carlos (IQSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
• Associated research grant: 14/50867-3 - INCT 2014: National Institute of Science and Technology in Bioanalysis, AP.TEM

Abstract

Although dementia affects more than 55 million people and is the seventh leading cause of death in the world and considered a public health priority by the WHO, research on the topic accounts for less than 1.5% of health production in the world. The most common type of dementia is Alzheimer's Disease (AD), whose therapy is being reconfigured due to the approval and integration of anti-amyloid monoclonal antibodies (mAbs). mAbs are recombinant protein drugs that bind to unique targets and are expensive. To reduce this cost, biosimilars are produced after the expiration of patents on innovative biologicals, being molecules similar to these, which require robust and direct analytical techniques that prove this similarity relationship. Post-Translational Modifications (PTMs) are chemical changes in proteins that can occur during the production of mAbs and that interfere with their biological function. Therefore, the identification of PTMs is important and carried out by peptide mapping. To this end, capillary electrophoresis coupled to mass spectrometry (CE-MS) is not the generally used method, but it has been validated due to its high separation efficiency and very low flow rates, which lead to greater efficiency in ion production, very high sensitivity and is less expensive. The study of CE-MS for the analysis of biopharmaceuticals in Brazil is scarce, practically non-existent, and the technique would be a new alternative. The study aims to use the CE-MS technique to perform peptide mapping and examine the biosimilarity of the PTMs obtained, comparing innovative mAbs, used for the treatment of dementia, with their biosimilars, not applied in the same therapy, in order to verify the potential of application of the least costly medication.