Covalent Bioscience – Alzyme

Summary

Covalent Bioscience, Inc. is producing Alzyme, a catalytic antibody (catabody) that destroys amyloid beta, a misfolded protein that forms Alzheimer’s plaques. The company is also developing prototype Tauzyme candidates to destroy misfolded tau protein, another amyloid implicated in Alzheimer’s disease.

Unlike conventional antibodies, these catabodies directly destroy amyloid beta and tau aggregates through chemical interactions, even when given briefly and at a low dose. The company reports that while antibody therapies increase inflammation, its catabody therapy decreases it. There is also a reported lack of off-target interactions, microbleeds, and glial activation in mouse models, suggesting that a future therapy may have few side effects in humans.

While catabody therapies do not affect the fundamental proteostasis issues that cause amyloid aggregates to form, the development of these therapies offers hope for people suffering from Alzheimer’s and other amyloid-related diseases.

References

[1] Planque, S.A., Nishiyama, Y., Sonoda, S., Lin, Y., Taguchi, H., Hara, M., Kolodziej, S., Mitsuda, Y., Gonzalez, V., Sait, H.B., Fukuchi, K., Massey, R.J., Friedland, R.P., O’Nuallain, B., Sigurdsson, E.M., Paul, S. Specific amyloid β clearance by a catalytic antibody construct. J Biol Chem. 2015;290(16):10229-41. PMCID: PMC4400338.
[2] Kou, J., Yang, J., Lim, J.E., Pattanayak, A., Song, M., Planque, S., Paul, S. and Fukuchi, K.I. Catalytic immunoglobulin gene delivery in a mouse model of Alzheimer’s disease: Prophylactic and therapeutic applications. Mol Neurobiol. 51(1):43-56, 2015. PMCID: PMC4198531.
[3] Nishiyama, Y., Taguchi, H., Hara, M., Planque, S.A., Mitsuda, Y., Paul S. Metal-dependent amyloid β-degrading catalytic antibody construct. J Biotechnol. 180:17-22, 2014. PMCID:PMC4512298.
[4] Paul, S., Planque, S., and Nishiyama, Y. Immunological origin and functional properties of catalytic autoantibodies to amyloid beta peptide. J Clin Immunol. 30 Suppl 1:S43-S49, 2010. PMCID:PMC3147076.
[5] Paul, S., Planque, S., and Nishiyama, Y. Beneficial catalytic immunity to amyloid β peptide. Proceedings of the Fourth Conference of Strategies for Engineered Negligible Senescence (SENS4). September 3-7, 2009. Queens’ College, Cambridge, United Kingdom. Rejuvenation Res. 13(2-3):179-187, 2010. PMCID:PMC2946056.
[6] Taguchi, H., Planque, S., Sapparapu, G., Boivin, S., Hara, M., Nishiyama, Y., and Paul, S. Exceptional amyloid β peptide hydrolyzing activity of non-physiological immunoglobulin variable domain scaffolds. J Biol Chem. 283(52):36724-36733, 2008. PMCID:PMC2606003.

Website: Covalent Bioscience