Biacore system used in study to show potential drug target for sleeping sickness causing parasites

The paper was published in Science, May 2008; 320: 677 – 681 and is the result of a collaboration between scientists at the Université Libre de Bruxelles, Belgium, and the University of Aarhus, Denmark.

A Biacore 3000 was used to examine binding parameters and properties of the parasite haptoglobin-hemoglobin (Hp-Hb) receptor TbHpHbR and its human functional analog CD163. The analysis showed that TbHpHbR binds the haptoglobin related protein-hemoglobin complex (Hpr-Hb) as well as Hp-Hb, unlike human CD163, suggesting that the parasite receptor is unable to discriminate between Hpr and Hp.

“The fact that the parasite actively uses a component of the host (hemoglobin) as a way to protect itself against the defenses of the host is an interesting facet of the biology of parasites. We discovered that the two subspecies of T. brucei that can infect humans both possess TbHpHpR,” said Dr. Etienne Pays, Université Libre de Bruxelles. “As the receptor shows equal affinity for the human-specific Hpr-Hb complex and the Hp-Hb complex, in contrast to the analogous human receptor CD163 which cannot bind Hpr-Hb, we deduce that TbHpHbR is a parasite-specific entry site for Hpr-Hb. Thus, the HprHb complex could be coupled to toxins and used as a novel drug against the parasite, targeting only the parasite and not the host.”

Dr. Søren Moestrup, University of Aarhus, commented: “Our next step is to contribute to the development of these new conjugate drugs, using the receptor as an entry point into the parasite. The assay using a Biacore system, developed during this investigation, will be essential for assessing binding of drug candidates to the receptor.”