Summary

Covalent Biosciences, Inc. is developing Cardizyme, a catabody that destroys transthyretin amyloid (misTTR) [1-2]. Amyloids are misfolded proteins that aggregate in harmful clumps and do not perform their original functions, and this amyloid is implicated in heart disease, spinal disorders, and other organ damage. It is one of the principal causes of death for supercentenarians, people who have lived longer than 110 years.

Unlike a conventional antibody, a catabody destroys amyloid directly rather than targeting it for the immune system. Therefore, it functions even when the immune system is malfunctioning and does not involve inflammation. The company reports that Cardizyme targets misTTR exclusively, having insignificant effects on properly folded transthyretin and other proteins.

While catabody therapies do not correct the fundamental loss of proteostasis that causes amyloid aggregates to form, the development of these therapies offers hope for people suffering from transthyretin amyloidosis and other amyloid-related diseases as periodic clearance offers a better option over the current standard of care.

References

[1] Planque, S.A, Nishiyama, Y., Hara, M., Sonoda S., Murphy, S.K., Watanabe, K., Mitsuda, Y., Brown, E.L., Massey, R.J., Primmer, S.R., O’Nuallain, B. and Paul, S. Physiological IgM class catalytic antibodies selective for transthyretin amyloid. J Biol Chem. 2014;289(19):13243-58. PMCID: PMC4036335.

[2] Phay, M., Blinder, V., Macy, S., Greene, M.J., Wooliver, D.C., Liu, W., Planas, A., Walsh, D.M., Connors, L.H., Primmer, S.R., Planque, S., Paul, S., O’Nuallain, B. TTR Aggregate Specific Antibodies Recognize Cryptic Epitopes on Patient-Derived Amyloid Fibrils. Rejuvenation Res. 17(2):97-104, 2014.