Diagnosis and Treatment of Arteriovenous Malformations

Tech ID: 29044 / UC Case 2017-003-0

Summary

UCLA researchers in the Departments of Molecular, Cell, and Development Biology & Surgery have identified Angiopoietin 2 (Ang-2) as a marker and potentially a strong contributing factor to the clinical presentation of pulmonary arteriovenous malformations.

Background

The Fontan procedure is used in pediatric patients who process only a single functional ventricle. After the Fontan circulation is established, some patients may develop pulmonary arteriovenous malformations (PAVMS) due to the unbalanced pulmonary perfusion of hepatic vein blood flow. Some of the symptoms for PAVMS include dyspnea, epistaxis, stroke and brain abscess. PAVMS is mainly diagnosed through radiography and CT scan. PAVMS was historically treated with surgical resection. With the technological advances, embolization has become the mainstay of treatment. Currently, no drug therapy is available for PAVMS.

Innovation

Researchers at UCLA identified Angiopoietin 2 (Ang-2) as a marker and potentially a strong contributing factor to the clinical presentation of PAVMS. Ang-2 level was significantly elevated (up to 10 fold) in patients who had a Fontan procedure. Ang-2 is an endothelial growth factor and a key regulator of angiogenesis and vessel maturation. It is known that Ang-2 level is significantly higher in patients with acute lung injury. Though antibodies against Angiopoietin 2 have been developed by both Regeneron and Amgen to suppress angiogenesis in cancer, the application of these antibodies to diagnose and treat PAVMS has not been disclosed in the literature.

Applications

Diagnosis and treatment of PAVMS: targeting Angiopoietin 2 with antibodies

Advantages

  • Clinical data is available in studies involved in suppression of angiogenesis
  • Potentially accelerated approval pathway

State Of Development

High levels of Angiopoietin 2 have been identified in patients who had a Fontan surgical procedure. Development is ongoing.

Related Materials

  • Shirali, A. S., et al. "Reproducible Arterial Denudation Injury by Infrarenal Abdominal Aortic Clamping in a Murine Model." Journal of visualized experiments: JoVE 117 (2016).
  • Glidewell, Steven C., et al. "Transcriptional impact of rare and private copy number variants in hypoplastic left heart syndrome." Clinical and translational science 8.6 (2015): 682-689.

Contact

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Inventors

  • Iruela-Arispe, Luisa

Other Information

Keywords

Angiopoietin 2, antibody, Fontan procedure, Hepatic factors, pulmonary arteriovenous malformations, PAVMS

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