Potential Cure for Sleeping Sickness
New Bar-Ilan University research has found the parasite's weak point and thus can pave the way for the development of a life-saving drug
The Trypanosoma brucei parasite is the cause for the Africa trypanosomiasis (sleeping sickness) disease, which, in its advanced stages, damages the nervous system and can be fatal without immediate treatment.
The disease is caused by a unicellular parasite that's transmitted to the blood of mammals through tik-tik (tsetse) flies, which are prevalent in Africa. In recent years, the disease also reached the West via travelers who were infected with the parasite. New Bar-Ilan University research has found the parasite's weak point and thus can pave the way for the development of a novel drug target.
Trypanosomes exist in mammalian blood in two forms: an active form that rapidly multiplies and a non-active form that lies dormant. The dormant form of the parasite is the one that will transform to the form that lives in the intestines of the tik-tik fly and continues the cycle of infection. New research discovered that the Achilles heel of the Trypanosoma parasite is during its transition between its two forms. The discovery may significantly advance the development for a cure of sleeping sickness.
Prof. Shulamit Michaeli, Vice President for Research and Development at Bar-Ilan University, has been researching the parasitic family to which Trypanosoma belongs for many years. Other diseases caused by the parasitic family include Chagas and Leishmaniasis, also known as the Rose of Jericho. Prof. Michaeli's research group, together with the research group of Prof. Luísa Figueiredo from IMM (Institute of Molecular Medicine in Lisbon) discovered a mechanism that could lead to the development of an RNA-based drug to treat sleeping sickness.
Their study revealed more than 1,400 long genes of the Trypanosoma parasite that do not encode a protein. One of these genes is processed into a smaller RNA molecule that is formed in the region of the cell's nucleus where the ribosomes are formed, i.e. the nucleolus. The researchers proved that the same nucleolar molecule serves two functions in the cell: it is involved in processing the ribosome and also controls genes that regulate the passage of the parasite in the blood during its transition between its active and dormant forms.
The researchers found that the overexpression of the small RNA molecule halted the development of the parasite and thus prevented the development of the disease in the blood of the mammal infected with it. This was the first known case of a nucleolar molecule whose role is to control the protein-encoding gene expression during the developmental phase. The discovery of RNA molecules of this type opens up a new channel for the development of drugs against the parasite that causes sleeping sickness. This discovery has large potential now, when RNA-based drugs are entering the clinical world.
Selectively injecting RNA into a parasite residing in the bloodstream is a challenging goal, but as this is a unique target molecule for the parasite, the drug will specifically target the parasite without fear of harming human cells, since this molecule doesn't exist or have targets in humans. This study is expected to encourage the examination of the role of such nucleolar RNAs in other parasites from the same family and even in different organisms.
The study, "A long noncoding RNA promotes parasite differentiation in African trypanosomes," was published in the Science Advances journal.