Trypanosomes, the parasites that cause sleeping sickness, dodge capture and destruction by the immune system by routinely altering their surface proteins to prevent recognition; however, a newly developed drug delivery strategy may defeat their stealth strategy.

The key to the trypanosome's disguise acumen is the variable surface glycoprotein (VSG), which undergoes constant alteration to help bloodstream parasites stay at least one step ahead of host immune detection. As a result, drug-based therapeutics are more practical than vaccination, but existing drugs bring with them the risk of severe toxicity and the potential for the emergence of drug-resistant strains.

Recent research has identified a naturally occurring human protein, apolipoprotein L-I (apoL-I), which is capable of inducing lysis in certain trypanosome strains. Now, in new work published in the May issue of Nature Medicine, Toya Nath Baral of the Vrije Universiteit Brussel (Belgium) and his colleagues describe a scheme for targeted delivery of this protein that seems to bypass the parasite's natural defense mechanisms.

The trypanosome species responsible for sleeping sickness is normally resistant to apoL-I, but a minor modification to this protein is enough to render these species vulnerable to destruction. For delivery, Baral and colleagues used a nanobody—a small, single-protein fragment derived from camel antibodies—that is capable of generically recognizing a variety of different VSGs. Linking modified apoL-I to this nanobody seemed to do the trick; in vitro, trypanosomes exposed to the conjugate perished completely, and in vivo, trypanosome-infected mice showed total clearance of parasites within a week of treatment. Mice receiving optimal doses of this therapeutic agent remained parasite-free and in apparently good health for the duration of the in vivo studies, as long as 60 d after treatment.

The authors indicate that the sequence similarity between nanobodies and human antibodies should lower the risk of unwanted host immune response for this therapy, and that this strategy may also prove useful for treating other infectious diseases.