Angiogenesis agent via VEGFR-2 Signaling Activation

Angiogenesis-inducing molecule derived from a novel angiogenesis factor, leading promise for therapeutic application in ischemic conditions or use as alternative VEGF reagent.

Advantages

  • Researchers have identified a novel angiogenic factor, BafA, secreted by Bartonella
  • This factor demonstrates high specificity, exclusively targeting vascular endothelial growth factor receptor 2 (VEGFR-2), thereby minimizing potential side effects without VEGFR-1 activation, which can contribute to hematogenous cancer metastasis.
  • VEGFR-2, pivotal in angiogenesis signaling, is anticipated to yield superior efficacy.

Technology Overview & Background

Therapeutic angiogenesis, involving the injection of angiogenic factors into ischemic regions to enhance blood circulation, is under active research and development, holding promise for treating ischemic ailments like myocardial infarction and arteriosclerosis obliterans. mRNA encoding VEGF-A, an endogenous angiogenic factor, had been developed as a therapeutic modality for heart failure.
Researcher focused on angiogenesis induced by Bartonella spp., uncovering a novel substance secreted by these bacteria that directly stimulates vascular endothelial cell proliferation, denoted as BafA (Bartonella angiogenic factor) (Nature Communications, 2020). BafA, an autotransporter found in Gram-negative bacteria, exhibits specificity for VEGFR-2 and activates the MEK-ERK pathway, thereby promoting vascular endothelial cell growth.
To promote drug development based on BafA, researchers cloned BafA homologs from over 30 Bartonella species, synthesizing recombinant proteins to assess their biological activity and structural integrity. This endeavor culminated in the development of novel BafA analogs, surpassing VEGF-A in activity, derived from various chimeric proteins combining these sequences.

Data

  • At 0.08 nM, the BafA analog demonstrated approximately 1.4-fold greater efficacy than VEGF-A in stimulating vascular endothelial cell proliferation.
  • BafA analogs exhibited superior potency in activating VEGFR2 signaling compared to VEGF-A.
  • In a murine model of leg ischemia, administration of 0.1 μg of BafA analog (i.m.) resulted in enhanced blood flow within the ischemic limb.

Patent

  • PCT/JP2023/008410
  • JP7229519

Principal Investigator & Academic Institution

Dr. Kentaro Tsukamoto (Specially Appointed Associate Professor, Research Institute for Microbial Diseases, Osaka University)

Expectations

TECH MANAGE CORP. is looking for a pharmaceutical company/start-up that is interested in the development of this novel angiogenesis agent. We can also arrange a meeting with the PI of this invention. Please feel free to contact us with any requests you may have.

 

 

Project.TT-04876

 

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