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A Method for Restoring BMP-Receptor Signaling in a Cell


05.01.2010 | Ref.Nr. 07154
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Life Science

BMP signaling is essential for developmental processes and tissue homeostasis and therefore highly regulated. Defects in BMP signaling can cause different disease as for example pulmonary arterial hypertension.

The inventors found that cGKI interacts with BRII and enhances the BMP receptor Smad signaling as a adaptor protein via a novel mechanism. The receptor regulated Smad proteins (R-Smad), Smads 1 and 5, are intracellular mediators of BMP signaling. These proteins translocate together with Smad4 to the nucleus.

Their they modulate transcription by binding to specific sequences on the promoters of target genes. It is suggested that cGKI stimulates Smad mediated BMP2 signaling and regulates gene expression of a transcriptional co-factor for Smads (Id1).

The increase in cGKI expression can compensate the defective BMP signaling cascade originating from a BRII mutant and restore the signaling pathway. The novel cGKI-based pharmaceuticals can be used to treat a cell, tissue or an organism with a disease or a condition that is associated with impeded or interrupted BMP-receptor signaling, insofar as the activity of cGKI is increased in the cell, tissue or organ to be treated

 

IP Rights
A PCT Application was filed on February 27, 2009 claiming priority of a European Patent Application filed on February 27, 2008.

Origin
The method was developed at the Freie Universität Berlin.

Application Area:
Pharma
Development Stage: In vivo
Type of Collaboration: License
Schlagworte: BMP, Cell, Organ, Protein, Receptor, Smad, Tissue,
Weitere Kategorien: Cardiology, Diagnostics, Life Science
Bild des Benutzers Dr. Bettina Büttner
Licensing Manager: Dr. Bettina Büttner
T +49 30 2125 4835
F +49 30 2125 4822
bettina.buettner@ipal.de
Market Potential: Worldwide
Benefits:
  • Method offers a additive for restoring or enhancing BMP receptor signaling
  • Knowing the meaning of an enhanced cGKI activity allows for targeted production of pharmaceuticals with a high cGKI fraction
  • Use BMP receptors to screen for substances for their cGKI activity
  • Use cGKI as detector to find receptors they can bind to and identifying & isolating the related proteins
  • cGKI can be used to transcriptional activate genes that have a BMP response element

Microginin Synthetase - Gene Cluster and Application in Biocombinatorics


11.02.2009 | Ref.Nr. 05130
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Life Science

The complete DNA sequence of the gene cluster coding for the microginin synthetase of the cyanobacterium Microcystis aeruginosa has been identified and sequenced for the first time. The microginin synthetase is a large multi-enzyme complex which catalyzes the microginin, a small linear lipopeptide belonging to the group of non-ribosomal synthesized peptides.

Microginins are synthesized by various species of cyanobacteria (“blue-green algae”) in diverse structure variants. Mircroginins represent an interesting group of unusual peptides in view of medical application as they are known to have inhibitory effects on the Angiotensin-Converting- Enzyme (ACE) . Thus microginins are potential ACE-inhibitors and represent important drug candidates to treat hypertension and associated diseases such as chronic heart failure and diabetic nephropathy.

The new identified DNA-sequence of the microginin synthetase gene cluster can be used to identify homologue gene cluster in other cyanobacteria species and as a matter of fact for the detection of new microginin variants or microginin-like structures. Further on, novel microginin variants can be generated by gene biocombinatoric experiments (gene shuffling) with the objective to optimize the ACE-inhibitory effect.

 

IP Rights
An European patent application has been filed on December 02, 2005 at the European Patent Office (EP05026396.1). A PCT patent application has been filed on December 01, 2006 at the European Patent Office (PCT/EP2006/011563).

Origin
This technology has been developed by Dr. Dan Kramer at the Humboldt University Berlin- Institute of Biology and the company Cyano-Biotech GmbH Berlin.

 

Application Area:
Pharma, Biotech
Development Stage: Concept
Type of Collaboration: License
Schlagworte: Angiotensin-Converting-Enzyme, Biocombinatorics, Cyanobacteria, DNA, Microginin Synthetase,
Weitere Kategorien: Cardiology, Diagnostics, Life Science
Bild des Benutzers Rafaela Kunz
Licensing Manager: Rafaela Kunz
T +49 30 2125 4825
F +49 30 2125 4822
rafaela.kunz@ipal.de
Market Potential: Worldwide
Benefits:
  • 10-30 % therapies of patients treated with currently available ACE-inhibitors are ineffective -> Novel  or improved ACE-inhibitors to treat hypertension are needed
  • Microginins are non-toxic and show ACE-inhibitory effects
  • Easy and effective method to identify microginin-producing strains of cyanobacteria
  • Easy method to generate novel non-natural microginins or microginin-like structures optimizing the ACE-inhibitory effect
  • Ongoing increasing R& D activities in the field of hypertension therapeutics
  • ACE-inhibitors belong to rank 9 of the Top10 of therapy classes (2002)