Value Proposition:
· Antibiotic treatment strategy for capillary malformations and Sturge-Weber Syndrome.
· Selectively targets endothelial cells with the pathogenic GNAQ mutations using puromycin
· Inhibits cell proliferation and reduces cell survival via activation of TRP6/NFAT signaling pathway
· Compatible with various drug administration strategies (oral, topical, injection, or ocular)
· Can be used in conjunction with laser treatment
· Broadly applicable for the treatment of diseases characterized by vascular malformation including uveal melanoma or Sturge-Weber syndrome
· Invention provides a novel transfected human embryonic kidney (HEK) and endothelial cell line containing pathogenic GNAQ mutations which can be used for drug-development and in-vitro assays
Unmet Need
Capillary malformations, including port-wine birthmarks, occur in about 1 in 300 live births, while Sturge-Weber syndrome, a vascular malformation syndrome involving the brain, skin, and eye, occurs in about 1 in 20,000 live births. Current treatments are primarily symptomatic and inadequate. These conditions, caused by the R183Q somatic mosaic mutation in GNAQ in endothelial cells, lack effective targeted therapies. There is an unmet need for innovative treatments that specifically address the molecular abnormalities underlying these vascular malformations.
Technology Overview
Johns Hopkins researchers identified that endothelial cells with the GNAQ mutation exhibit increased sensitivity to the antibiotic puromycin. This discovery suggests a novel therapeutic approach using puromycin, its analogues, or its inhibitors to target these mutated cells. Researchers have found that puromycin treatment leads to abnormal TRPC6/NFAT signaling pathway in human embryonic kidney and human endothelial cells transfected with GNAQ mutations. Data from these cells treated with puromycin show reduced proliferation and decreased cell survival, indicating that puromycin antibiotic treatment maybe a viable therapeutic strategy of patients with GNAQ mutations and capillary malformations.
Stage of Development
In vitro Testing
Publications
1. Shirley MD, Tang H, Gallione CJ, Baugher JD, Frelin LP, Cohen B, North PE, Marchuk DA, Comi AM, Pevsner J. Sturge-Weber syndrome and port-wine stains caused by somatic mutation in GNAQ. N.Engl.J.Med. 2013 May 23;368(21):1971-9. PMCID:PMC3749068
