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Z6*

Prevention of fibrosis and organ protection by preconditioning cells via ARNT regulation

Prof. Michael Zeisberg, University Medical Center Goettingen; Prof. Elisabeth Zeisberg, University Medical Center Goettingen; Dr Björn Tampe, University Medical Center Goettingen; Dr Desiree Tampe, University Medical Center Goettingen; Prof. Gerhardt Anton Müller, University Medical Center Goettingen

MBM ScienceBridge


Challenge

Injury in an organ triggers a complex signaling cascade that involves various cellular and molecular responses, ultimately culminating in tissue fibrosis, loss of functional parenchyma and organ failure. Progressive fibrosis and impaired regenerative capacity is still an unmet biomedical challenge, because once chronic lesions have manifested, no effective therapies are available as of yet for clinical use. (i.e. progression of chronic kidney disease (CKD) towards end-stage renal disease (ESRD)). It has been known that parenchymal organs including the kidney can be preconditioned to resist later acute ensuring tissue injuries, preventing both progressive loss of functional epithelium and kidney fibrosis.


Technology

The technology is based on a novel signaling axis, which through the increase of the expression of ALK3 controls the BMP signaling response, which ultimately has an anti-fibrotic and pro-regenerative action. These effects protect an organ against chronic injury, progressive loss of functional parenchymal cells, or fibrosis.

Examples are:

1. Inhibitors of protein phasphatase 2A, for example LB-100, which reduces tubulointerstitial fibrosis and attenuates chronic kidney failure.
2. Inhibitors of the transcriptional repressor complex FKBP12/YY1 like tacrolimus (FK506) or GPI-1046, which protects from chronic kidney injury and chronic renal failure, respectively


Commercial Opportunity

The technology allows for setting up a therapy against chronic injuries, both for prevention of chronic injuries as well as for an acute therapy, if the injury is already established.


Development Status

An in vivo proof of concept successfully achieved for several targets. Some of the tested drugs are already in clinics.


Patent Situation

We filed PCT international IP rights in the name of the Georg-August-Universität Göttingen, University Medical Center, and are looking for a licensing partner, who develops and markets a product.


Further Reading

Tampe et al.: J Clin Invest. 2018: Pharmacological induction of hypoxia-inducible transcription factor ARNT attenuates chronic kidney failure


 

Prevention of fibrosis and organ protection by preconditioning cells via ARNT regulation