AI Article Synopsis

  • Lecanemab is a monoclonal antibody designed to target amyloid beta in Alzheimer's disease, with its short half-life influenced by plasma protein interactions.
  • The study investigated how lecanemab binds to plasma proteins, with a focus on its biosimilar, using techniques like ELISA and Western blotting.
  • Results showed that fibrinogen is a binding partner for lecanemab, potentially affecting the availability of free antibodies in the bloodstream and highlighting the importance of plasma protein binding in therapeutic antibody treatment for neurodegenerative diseases.

Article Abstract

Objective: Recombinant monoclonal therapeutic antibodies like lecanemab, which target amyloid beta in Alzheimer's disease, offer a promising approach for modifying the disease progression. Due to its relatively short half-life, Lecanemab, administered as a bi-monthly infusion (typically 10mg/kg) has a relatively brief half-life. Interaction with abundant plasma proteins binder in the bloodstream can affect pharmacokinetics of drugs, including their half-life. In this study we investigated potential plasma protein binding interaction to lecanemab using lecanemab biosimilar.

Methods: Lecanemab biosimilar used in this study was based on publicly available sequences. ELISA and Western blotting were used to assess lecanemab biosimilar immunoreactivity in the fractions human plasma sample obtained through size exclusion chromatography. The binding of lecanemab biosimilar to candidate binders was confirmed by Western blotting, ELISA, and surface plasmon resonance analysis.

Results: Using a combination of equilibrium dialysis, ELISA, and Western blotting in human plasma, we first describe the presence of likely plasma protein binding partner to lecanemab biosimilar, and then identify fibrinogen as one of them. Utilizing surface plasmon resonance, we confirmed that lecanemab biosimilar does bind to fibrinogen, although with lower affinity than to monomeric amyloid beta.

Conclusion: In the context of lecanemab therapy, these results imply that fibrinogen levels could impact the levels of free antibodies in the bloodstream and that fibrinogen might serve as a reservoir for lecanemab. More broadly, these results indicate that plasma protein binding may be an important consideration when clinically utilizing therapeutic antibodies in neurodegenerative disease.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11092601PMC
http://dx.doi.org/10.1101/2024.05.01.591892DOI Listing

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