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Vantage Biosciences is dedicated to unlocking the potential of cutting-edge science to address inflammatory conditions driven by leukocyte trafficking and oxidative stress

AOC-3 has a dual functionality, promoting leukocyte migration and generation of pro-inflammatory mediators.

AOC-3 is a semicarbazide sensitive amine oxidase enzyme (SSAO) expressed on the surface of vascular endothelial cells where it facilitates the adhesion of circulating leukocytes and their subsequent transmigration into tissues. It also catalyses the oxidative deamination of primary amines to produce toxic aldehydes in the surrounding tissue.

Catalytic function of AOC-3
Diagram showing the catatlytic function of AOC-3
The role of AOC-3 in the transmigration of leukocytes
Diagram showing the role of AOC-3 in the transmigration of leukocytes
Human eye anatomy, retina, optic disc artery and vein

AOC-3 in non-proliferative diabetic retinopathy

Ammonia, aldehydes, and reactive oxygen species are released as a result of the interaction between AOC-3 and its substrates. These contribute to inflammation and the accumulation of leukocytes, which ruptures blood vessels and leads to ischemia.

AOC-3 inhibition reduces leukocyte recruitment and decreases the production of reactive oxygen species, thereby correcting the underlying hypoxia, ischemia, and oedema seen in diabetic retinopathy, as well as improving vascular function.

Human eye anatomy, retina, optic disc artery and vein

AOC-3 in non-proliferative diabetic retinopathy

Ammonia, aldehydes, and reactive oxygen species are released as a result of the interaction between AOC-3 and its substrates. These contribute to inflammation and the accumulation of leukocytes, which ruptures blood vessels and leads to ischemia.

AOC-3 inhibition reduces leukocyte recruitment and is predicted to decrease the production of reactive oxygen species, thereby correcting the underlying hypoxia, ischemia, and oedema seen in diabetic retinopathy, as well as improving vascular function.

Underlying data is supportive of this approach:

  • Elevated levels of soluble AOC-3 have been found in the serum of diabetic patients1,2 and in the vitreous fluid of patients with PDR3
  • Enzymatic oxidation of amines generates local pro-inflammatory microenvironment, inhibition of AOC-3 reduces the concentration of reactive oxygen species4
  • Inhibition of AOC-3 with VX-01 significantly decreases leukocyte infiltration within the retina
  • VX-01 significantly improves ocular hyperpermeability and lens opacity in preclinical models
  • Luo W, Xie F, Zhang Z, Sun D. Vascular adhesion protein 1 in the eye. J Ophthalmol. 2013;2013:925267
  • Yoshikawa N, Noda K, Shinoda H, Uchida A, Ozawa Y, Tsubota K, Mashima Y, Ishida S. Serum vascular adhesion protein-1 correlates with vascular endothelial growth factor in patients with type II diabetes. J Diabetes Complications. 2013 Mar-Apr;27(2):162-6. doi: 10.1016/j.jdiacomp.2012.09.001. Epub 2012 Oct 11. PMID: 23062326
  • Murata M, Noda K, Fukuhara J, et al. Soluble vascular adhesion protein-1 accumulates in proliferative diabetic retinopathy. Invest Ophthalmol Vis Sci. 2012;53(7):4055–62
  • Murata M, Noda K, Kawasaki A, Yoshida S, Dong Y, Saito M, Dong Z, Ando R, Mori S, Saito W, Kanda A, Ishida S. Soluble Vascular Adhesion Protein-1 Mediates Spermine Oxidation as Semicarbazide-Sensitive Amine Oxidase: Possible Role in Proliferative Diabetic Retinopathy. Curr Eye Res. 2017 Dec;42(12):1674-1683. doi: 10.1080/02713683.2017.1359847. Epub 2017 Sep 22. PMID: 28937866

AOC-3 in primary sclerosing cholangitis

Through its catalytic function, AOC-3 induces MAdCAM-1 expression by endothelial cells, which enhances leukocyte adhesion and transmigration. In healthy individuals, MAdCAM-1 expression is restricted to the gut.

In PSC it is also detected on hepatic endothelium where it promotes recruitment of mucosal α4β7+ T cells to the liver, provoking an inflammatory response.

Anti-AOC-3 antibodies that have been clinically tested do not suppress oxidase activity - an important feature of the pathological role of AOC3 in PSC. VX-01 has a dual mechanism targeting leukocyte trafficking and pro-inflammatory products of local amine oxidation.

An image of an inflamed liver in the human body

AOC-3 in primary sclerosing cholangitis

Through its catalytic function, AOC-3 induces MAdCAM-1 expression by endothelial cells, which enhances leukocyte adhesion and transmigration. In healthy individuals, MAdCAM-1 expression is restricted to the gut.

In PSC it is also detected on hepatic endothelium where it promotes recruitment of mucosal α4β7+ T cells to the liver, provoking an inflammatory response.

Anti-AOC-3 antibodies that have been clinically tested do not suppress oxidase activity - an important feature of the pathological role of AOC3 in PSC. VX-01 has a dual mechanism targeting leukocyte trafficking and pro-inflammatory products of local amine oxidation.

An image of an inflamed liver in the human body.

Underlying data is supportive of this approach:

  • sAOC-3 is significantly higher in individuals with PSC vs a healthy control, and sAOC-3 titre is strongly predictive of clinical outcome in PSC
  • AOC-3 is a recognised driver of acute and chronic tissue inflammation and fibrosis in multiple animal models
  • Pharmacological inhibition or AOC-3 KO significantly reduces tissue leukocyte infiltration and disease histopathology
  • sAOC-3 and tissue AOC-3 is significantly elevated in human NAFLD; sAOC-3 is independently associated with the presence of liver disease
  • AOC-3 inhibition has been shown to significantly decrease key liver biomarkers in NAFLD