Friday, 17 Jan 2020

You are here

VEGF121-Fibrin as a Potential Therapy for Skin Ulcers in Systemic Sclerosis

The etiology of systemic sclerosis (SSc) remains unclear, but appears to involve complex pathogenic interactions between the immune system, the vasculature and fibrotic processes. Better understanding of such interactions could lead to discovery of new therapeutic approaches, and requires appropriate animal models.

The University of California at Davis chicken lines 200 and 206 are one such animal model displaying all hallmarks of SSc. While SSc is characterized by uncontrolled overexpression of vascular endothelial growth factor (VEGF), this results in chaotic vessels and the cutaneous ulcerations. 

In this animal model study, it was hypothesised that local administration of VEGF121-fibrin and consequent cell demanded release of VEGF from the fibrin matrix would overcome the uncontrolled VEGF expression found in SSc, and induce sufficient angiogenesis to heal and prevent ischemic ulcers.

Ninety-one early and late ischemic comb and neck skin lesions of UCD-206 chickens were treated locally with VEGF121-fibrin, fibrin alone, or left untreated. After 1 week of treatment the clinical outcome was assessed. Angiogenesis was studied by immunofluorescence staining of vascular markers quantitatively analyzed using TissueQuest.

Overall, 79.3% of the VEGF121-fibrin treated lesions showed clear clinical improvement, whereas 71.0% of fibrin treated controls and 93.1% of untreated lesions had deteriorated.

The study results suggest that VEGF121 from fibrin matrix induces controlled angiogenesis by differential regulation of VEGFR-1 and VEGFR-2 expression, shifting the balance towards the pro-angiogenic VEGFR-2. The study shows the potential of covalently conjugated VEGF-fibrin matrices for the treatment of ischemic lesions such as fingertip ulcers.  The long-term effects and potential side effects of VEGF121 will require further clinical study.

Dr. Olga Petryna
The author has no conflicts of interest to disclose related to this subject

Add new comment

More Like This

TULIP2 - Anifrolumab Succeeds in Lupus

NEJM has published the results of the TULIP2 trial with anifrolumab, an alpha interferon blocker, in the treatment of systemic lupus erythematosus, showing significant improvement (over placebo) in multiple lupus outcome measures, including BICLA, SRI-4, CLASI and others.

Steroids Up the Risk of Organ Damage in SLE

Lancet Rheumatology has reported the results of a multicenter follow-up study of systemic lupus erythematosus (SLE) patients showing that organ damange is linked to glucocorticoid use, independent of clinical or serological disease activity.

Treatment of Statin-induced anti-HMGCR myopathy

Statin-induced myositis, often with anti-HMGCR autoantibodies can be difficult to manage, Arthritis Research & Therapy yhas published the experience of 55 patient with HMGCR myopathy, demonstrating that while steroid management may be reasonable in select patients, the use of triple steroid/IVIG/SSI was very efficacious in induction.

Best of 2019 - 2019 EULAR Guidelines on Antiphospholipid Syndrome Management

A EULAR task force has reviewed the medical literature and developed evidence-based recommendations for the management of antiphospholipid syndrome (APS) in adults. They note that a high-risk antiphospholipid antibody (aPL) profile is associated with greater risk for thrombotic and obstetric APS.

Best of 2019 - New EULAR/ACR Classification Criteria for SLE

The European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR) have jointly developed new classification criteria for systemic lupus erythematosus (SLE); prompted by the need for criteria that were both highly sensitive and specific. The net result is improved sensitivity and specificity, but the use of positive ANA requirement along with a longer list of weighted criteria ensures its utility in SLE research (including early or latent SLE), but not clinical practice.