African sleeping sickness is a disorder caused by the trypanosome parasite. The blood-sucking tsetse fly transmits the parasite from person to person. Once someone has been infected by the parasite, the person's body has great difficulty getting the infection under control, because the parasite constantly changes appearance. Thus, the trypanosome remains impervious to the antibodies that the body produces.
Parasite eludes human defense mechanism
Fortunately, our body has a special defense mechanism that can help us in the fight against African trypanosomes. Our blood contains ApoL-1, which is toxic to − and neutralizes − most types of trypanosomes.
However, there is one trypanosome against which we are not protected: Trypanosoma brucei rhodesiense. This parasite is resistant to ApoL-1, because it has particular proteins that counteract ApoL-1's action.
For some time now, scientists have known that a variant of ApoL-1 is not neutralized by Trypanosoma brucei rhodesiense. This truncated ApoL-1 variant can help to overcome the parasite that infects our body, but only when it is present in very high concentrations. The challenge for the researchers was to get this truncated ApoL-1 variant efficiently to the place where it is needed: onto the surface of the parasite.
Nanobody carries ApoL-1 variant to the parasite
Under the direction of Serge Muyldermans and Patrick De Baetselier, VIB researchers have previously produced a nanobody (a very small antibody) that targets and binds to the parasite very specifically (Stijlemans et al., 2004). Toya Nath Baral and his VIB colleagues have now succeeded in coupling this nanobody to the abbreviated ApoL-1 variant. This creates a special product that binds immediately to the parasite and thus brings the ApoL-1 variant to the place where it can carry out its neutralizing action.
All the tests performed on mice have been very promising: Trypanosome-infected mice survive after 1 treatment. The parasite is removed from the blood and all effects associated with the disease disappear. There is every indication that this substance can also counteract Trypanosoma brucei rhodesiense in humans − sparing them from African sleeping sickness.
Given that this research can raise a lot of questions for patients, we ask you to please refer questions in your report or article to the email address that VIB makes available for this purpose: patienteninfo@vib.be. Everyone can submit questions concerning this and other medically-oriented research directly to VIB via this address.
This research was accomplished through an intense collaboration between VIB and the Free University of Brussels (VUB and ULB).
Nature Medicine