Challenge

Idiopathic systemic capillary leak syndrome (ISCLS) is a serious and life-threatening disorder. It is characterized by recurrent episodes of severe fluid leakage from blood vessels, leading to hypovolemic shock and organ failure. The exact cause of this rare condition is not fully understood. However, it is believed that viral diseases can trigger relapses in some patients. Treatment options for acute flares of ISCLS are currently limited to supportive care. This means that there is no specific treatment available to target the underlying cause of the condition. This is further complicated by the fact that ISCLS is often misdiagnosed as hypovolemic shock due to its rarity, with only around 200 cases reported worldwide. Doctors are urging caution and special attention for patients with Clarkson’s disease during viral outbreaks. Viral infections, including COVID-19 and influenza, can worsen symptoms and lead to severe, refractory episodes in these vulnerable patients. In response to these challenges, FX06, a new peptide drug, is being tested to reduce capillary leak in patients who develop Acute Respiratory Distress Syndrome – induced by viruses, bacteria and trauma. This approach might be beneficial also for  Clarkson’s patients. More research is urgently needed on FX06 and other treatments for this rare, dangerous syndrome exacerbated by viral infections.

Solution

This study of the researchers from the Luigi Sacco University Hospital of Milan aimed to explore the impact of FX06 on the barrier function of endothelial cells when exposed to intercritical and acute sera from ISCLS patients. The results demonstrated promising findings, indicating the potential effectiveness of this drug in targeting the underlying pathophysiological mechanisms of ISCLS. This could prove to be a significant breakthrough in managing this dangerous condition, as FX06 exhibited potential in restoring the compromised endothelial barrier function during critical ISCLS crises.

The key findings of the research:

• Restored endothelial function: FX06 effectively improved endothelial barrier function in vitro when endothelial cells were incubated with serum from Clarkson patients with acute flares.
• Advanced research methods: Using the transwell permeability assay and three-dimensional microfluidic devices, the study provides comprehensive insights into the mechanism of FX06 and shows how it targets the underlying pathophysiological mechanisms of Clarkson disease.
• Focus on VE-cadherin: FX06 specifically enhanced the cellular localisation of VE-cadherin, which is essential for endothelial cell adhesion.
• Independent of nitric oxide: The changes in endothelial permeability were found to be independent of nitric oxide, adding a new dimension to the understanding of ISCLS.