Tardigrade DSUP protein for use in the therapeutic treatment of diabetes

Leveraging the protective properties of the tardigrade “Damage Suppressor Protein” (DSUP) from Ramazzottius varieornatus against DNA damage, this method uses DSUP in pancreatic beta cells to protect them from the inflammatory and oxidative stress that drives their death during type 1 diabetes.

DSUP, which is known to reduce oxidative stress-induced DNA fragmentation and thereby limit cell death, was stably introduced into murine insulinoma MIN6 cells using a DSUP-encoding plasmid. The resulting DSUP+ cells survive free-radical–mediated stress following hydrogen peroxide (H₂O₂) treatment. Moreover, the protection conferred by DSUP was confirmed in response to pro-inflammatory stress typical of type 1 diabetes, induced by a cytokine cocktail (IL-1β, TNFα, and IFNγ), which reduced apoptosis while preserving endogenous insulin secretory capacity.

Finally, it was shown that DSUP mRNA, transiently introduced into human EndoC-βH1 beta cells, is sufficient to produce the full-length protein.

This therapeutic tool, aimed at protecting insulin-producing beta cells from immune-mediated damage, may be used either as a recombinant protein or by delivering the nucleotide sequence encoding DSUP (e.g., via DNA- or RNA-based expression).