Pantethine Protects Brain from Malaria Infection

Byron's Comments:

The method used by pantethine to protect the brain of animals in this experiment is very good news for humans, as a compromised blood brain barrier leads to all manner of cognitive decline and other nerve-related issues.

Study Title:

Protection against cerebral malaria by the low-molecular-weight thiol pantethine.

Study Abstract:

We report that administration of the low-molecular-weight thiol pantethine prevented the cerebral syndrome in Plasmodium berghei ANKA-infected mice. The protection was associated with an impairment of the host response to the infection, with in particular a decrease of circulating microparticles and preservation of the blood-brain barrier integrity. Parasite development was unaffected. Pantethine modulated one of the early steps of the inflammation-coagulation cascade, i.e., the transbilayer translocation of phosphatidylserine at the cell surface that we demonstrated on red blood cells and platelets. In this, pantethine mimicked the inactivation of the ATP-binding-cassette transporter A1 (ABCA1), which also prevents the cerebral syndrome in this malaria model. However, pantethine acts through a different pathway, because ABCA1 activity was unaffected by the treatment. The mechanisms of pantethine action were investigated, using the intact molecule and its constituents. The disulfide group (oxidized form) is necessary to lower the platelet response to activation by thrombin and collagen. Thio-sensitive mechanisms are also involved in the impairment of microparticle release by TNF-activated endothelial cells. In isolated cells, the effects were obtained by cystamine that lacks the pantothenic moiety of the molecule; however, the complete molecule is necessary to protect against cerebral malaria. Pantethine is well tolerated, and it has already been administered in other contexts to man with limited side effects. Therefore, trials of pantethine treatment in adjunctive therapy for severe malaria are warranted.

Study Information:

Penet MF, Abou-Hamdan M, Coltel N, Cornille E, Grau GE, de Reggi M, Gharib B. Protection against cerebral malaria by the low-molecular-weight thiol pantethine. Proc Natl Acad Sci U S A. 2008 January 105(4):1321-6.
Centre de Résonance Magnétique Biologique et Médicale, Unite Mixte de Recherche Centre National de la Recherche Scientifique 6612, Université de la Méditerranée, 13005 Marseille, France.

Full Study:

http://www.pnas.org/content/105/4/1321