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Researchers at New York University Grossman School of Medicine, led by Erin E. Congdon, have explored the potential of single domain antibodies (sdAbs) in treating tauopathies, including Alzheimer’s disease. The results of their study were recently published in The Lancet® and focused on the impact of different IgG subclasses on the efficacy and safety of sdAbs commonly known as Nanobodies® targeting pathological tau proteins. Derived from llamas immunized with tau proteins, these sdAbs were tested in primary cell cultures and JNPL3 tauopathy mice to determine which IgG subclass offers the best balance of efficacy and safety.
The findings reveal that unmodified sdAbs are non-toxic and effectively block tau toxicity and promote tau clearance. However, the efficacy and safety profiles of the Fc-(sdAb)2 subclasses varied. Some subclasses with effector functions were more effective in clearing tau, while others stabilized a toxic tau conformation, potentially worsening the condition. This highlights the importance of careful antibody design to avoid exacerbating tau pathology. Overall, the study suggests that tau antibodies with effector functions are generally safer and more effective, providing valuable insights for developing more effective treatments for neurodegenerative diseases.
This research was funded by the National Institute of Health and the NYU Alzheimer’s Disease Center Pilot Grant Program, underscoring the significant support for advancements in neurodegenerative disease research. The insights gained from this study guide the creation of safer and more effective tau immunotherapies, offering hope for better management of tauopathies.
ProSci’s Custom Antibody Services were used to develop the sdAbs used in this study. Tau target proteins were provided by the Sigurdsson lab and immunized into llamas. ProSci’s expertise with phage-display technologies was used to isolate sdAb binders against the target proteins. Single domain antibodies were originally produced in E. coli and further characterized by the customer. The entire process typically takes three months of immunization followed by three months of library construction, selection, and screening. ProSci has over a 95% success rate in developing sdAbs.
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Reference
- Congdon EE, Pan R, Jiang Y, Sandusky-Beltran LA, Dodge A, Lin Y, Liu M, Kuo MH, Kong XP, Sigurdsson EM. Single domain antibodies targeting pathological tau protein: Influence of four IgG subclasses on efficacy and toxicity. EBioMedicine. 2022 Oct;84:104249. doi: 10.1016/j.ebiom.2022.104249. Epub 2022 Sep 10. PMID: 36099813; PMCID: PMC9475275.
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