Defibrotide

Cerebral malaria (CM) is a severe manifestation of Plasmodium falciparum infection, characterized by seizures and coma, respiratory distress, hypoglycemia, and acidosis. Intensely studied for decades, important advances in understanding this clinically complex syndrome have been achieved, but highly efficacious treatment remains elusive.1 Even with rapid delivery of antimalarial drugs on diagnosis and the best supportive care, many CM victims do not survive.1 An effective malaria vaccine to prevent CM and other severe malaria syndromes is not yet available, making continued efforts to identify novel therapies, particularly those that can serve as adjuncts to antimalarial drugs, essential.2 Defibrotide (DF), a mixture of single-stranded ≈50-mer DNA aptamers with a minor component of double stranded DNA that is derived from depolymerized mammalian genomic DNA,3–5 is an exciting potential new recruit to the ranks of such adjunctive treatments. This multipotent drug displays endothelial-protective, antiischemic, anti-inflammatory, and mild anticoagulant effects and has been successfully used to treat comatose children experiencing veno-occlusive disease.3–5See accompanying article on page 786CM develops when mature intraerythrocytic stages of P. falciparum adhere to the brain microvasculature, interrupt normal blood flow, and promote endothelial activation, culminating in disruption of normal vascular function1 (Figure). Intense systemic and local inflammatory responses are believed to be important players in disease pathogenesis,6 and more recently, a role for dysregulated hemostasis has also been suggested.7,8 Francischetti et al identified a potential role for tissue factor (TF) in CM9 and argued that the TF-mediated coagulation-inflammation cycle underlies the pathogenesis of this disease.7,8 In this issue of Arteriosclerosis, Thrombosis, and Vascular Biology , Francischetti et al10 advance our understanding of malarial parasite/host interactions in this context. They argue that effective treatment of CM will require control of multiple …