A couple of months ago, an article was published in a scientific journal reporting encouraging lab results using a monoclonal antibody called 4E2, which targets the endothelial receptor tyrosine kinase Tie2 in SCLS patient-derived endothelial (capillary) cells. Once the molecule binds to the receptors, it promotes the normalization and stabilization of leaky blood vessels.

To evaluate 4E2 as a candidate for the treatment of SCLS, scientists first studied its effects on endothelial cells obtained from blood from patients with SCLS during convalescent periods and from healthy controls.

To determine the significance of these findings for vascular leakage in live animals, the authors then examined the impact of 4E2 on the skin microvasculature of mice challenged with classical permeability provocateurs, specifically histamine and influenza infections.

Mice are unusually susceptible to vascular leakage, particularly in peripheral tissues such as skin and skeletal muscle, after exposure to histamine and viral infections, and many of them die. Yet systemic injection of 4E2 into mice significantly attenuated the vascular leakage in their skin that had been induced by the injection of histamine. While a majority (80%) of the mice pretreated with a control substance before histamine administration had died within 30 minutes, nearly 65% of the mice pretreated with 4E2 remained alive 30 minutes later.

Further studies will be needed to determine the efficacy of 4E2 as IVIG-sparing prophylactic therapy in SCLS.

4E2 was developed by PharmAbcine Inc., a clinical-stage biotech company in South Korea focusing on the development of next-generation antibody therapeutics. The study was conducted in collaboration with Dr. Kirk Druey, Chief of the NIH's Lung and Vascular Inflammation Section, and the world’s leading researcher of SCLS.

This pioneering work was supported by the Division of Intramural Research, NIAID/NIH (grant AI001083-14 to Dr. Druey) and by a Collaborative Research and Development Agreement (CRADA) between NIAID/NIH and PharmAbcine Inc.

The article, titled "A ligand-independent Tie2-activating antibody reduces vascular leakage in models of Clarkson Disease,” highlights the significance of Tie2 activation and its potential implications for the treatment of SCLS. It has been added to the Disorder Resources section of our community, https://rareshare.org/communities/systemic-capillary-leak-syndrome#disorder_resources   The (highly technical) article is freely available at https://www.science.org/doi/10.1126/sciadv.adi1394

Because of the potential of PMC-403 to prevent or treat episodes of SCLS in humans is there, in February 2023, the US FDA granted Orphan Drug Designation (ODD) for PMC-403 for the treatment of Systemic Capillary Leak Syndrome.

This is amazing news.  Thanks so much for sharing and breaking it down :-).  This community with the leadership of Dr. Druey keep pushing forward to find effective treatments to help those who suffer lead longer fuller lives.  So thankful for all the efforts and dedication these medical experts have put in.

 

This is great news. I'm especially happy to think that one of the 18 vials of blood I gave Dr. Druey a few years ago contributed to this study!

Do we know how 4E2 is administered? Infusion, injection, other? I read the free article (skipping the most technical sections) but couldn't figure it out. Thanks!

Thank you so much for sharing this hopeful news! I feel like Dr. Druey is an absolute hero for continuing to persue understanding of and treatment for SCLS. This makes me proud that he is originally from Northern California, as am I :)
:D
Cathy