University of Texas System

Georg-august-universitaet Goettingen Stiftung Oeffentlichen Rechts, Universitaetsmedizin

Georg-august-universität Göttingen Stiftung Öffentichen Rechts, Universitätsmadizin

Georg-august-universitat Gottingen Stiftung Offentlichen Rechts, Universitatsmedizin

Elisabeth Zeisberg

Raghu Kalluri

Michael Zeisberg

Désiree Tampe

Gerhard Anton Mueller

Bjoern Tampe

Xu Xingbo

Xingbo Xu

Gerd Hasenfuss

Björn Tampe

Xiaoying Tan

Miriam Puls

Karl Toischer

Claudius Jacobshagen

The present disclosure is directed to novel therapeutic approaches for the prevention, treatment and/or delaying progression of chronic injury, progressive loss of functional parenchymal cells, or fibrosis of an organ. Specifically disclosed are agents for use in increasing homodimer-formation of ARNT in an organ in the prevention, treatment and/or delaying progression of chronic injury, progressive loss of functional parenchymal cells, or fibrosis of said organ, as further defined in the claims. In embodiments, said agent may be (i) an inhibitor of protein phosphatase 2A (PP2A) activity, (ii) an inhibitor of the transcriptional repressor complex FKBP12/YY1, or (iii) an expression construct, which is capable of over-expressing ARNT in said organ, as well as combinations of (i), (ii), and/or (iii).

Prevention or treatment of chronic organ injury

A method for re-expression of hypermethylated RASAL1, hypermethylated LRFN2, and hypermethylated KLOTHO based on an inactivated CRISPR-based system and a DNA dioxygenase as well as a gRNA guiding the construct to the RASAL1, LRFN2, and KLOTHO gene for demethylation of hypermethylated RASAL1, hypermethylated LRFN2, and hypermethylated KLOTHO, in particular, hypermethylated RASAL1, LRFN2, and KLOTHO promoter, thus, allowing re-expression of RASAL1, LRFN2, and KLOTHO for the treatment of fibrosis, cancer or neuronal disorders in a subject is provided. A kit of parts for allowing re-expression of hypermethylated RASAL1, hypermethylated LRFN2, and hypermethylated KLOTHO in a subject, a vector or vector system, and nucleic acid constructs are also provided.

Method for re-expression of different hypermethylated genes involved in fibrosis, like hypermethylated RASAL1 and use thereof in treatment of fibrosis as well as kit of parts for re-expression of hypermethylated genes including RASAL1 in a subject

Provided is a method of preventing, treating or delaying progression of a disease involving aberrant fibroblast proliferation. The method involves using a compound that reduces the level of tyrosine phosphatase activity effected by the protein EYA1A in the parenchymal organ, a nucleic acid ligase IV inhibitor, or an antisense oligonucleotide against the p53-binding protein 1 (53BP1).

Treatment of aberrant fibroblast proliferation

Growing community of inventors

Goettingen, Germany

Elisabeth Zeisberg