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Scientists believe that by genetically engineering a parasite called Toxoplasma gondii they will be better able to deliver drugs across the blood-brain barrier and into the brain.
“One of the biggest challenges in treating neurological diseases is getting through the blood-brain barrier (BBB),” said Oded Rechavi, PhD, professor at Tel Aviv University and lead author of the study published in the journal Nature Microbiology. “It is very difficult to deliver drugs to the brain via the bloodstream, and this is especially true for large molecules such as proteins, the critical ‘machines’ that carry out many important functions inside the cell.”
Toxoplasma gondii is a parasitic protozoan that can infect almost all warm-blooded animals.
In rodents, T. gondii alters their behavior, causing them to forget their fear of cats.
In humans, it is generally harmless, but can develop into a disease called toxoplasmosis which can result in a variety of neuropsychiatric conditions. It has also been discussed as a potential cause for a zombie outbreak in human beings.
“Most people don’t even feel the infection or only experience mild flu-like symptoms,” Rechavi explained. “The parasite is, however, dangerous for people with immune failure due to conditions like AIDS, and for fetuses whose immune system has not yet developed. This is why pregnant women are advised not to eat raw meat which might contain the parasite, and to stay away from cats, who might deliver it through their feces. While ridding the body of the parasite, a healthy immune system has only limited access to the brain, and the parasite remains in the brain throughout the carrier’s lifetime.”
Toxoplasma gondii, a protozoan brain parasite, has co-evolved with its various hosts, including humans, to target the brain. On infection, which is commonly oral, T. gondii can either travel to the brain by itself or ‘trick’ immune cells into carrying it there. In addition, Toxoplasma harbours specialized protein secretion organelles, such as rhoptries and dense granules, which it uses to furnish and adapt the cells in which it resides to support its persistence. In our study, we show that these mechanisms can be hijacked to transform Toxoplasma into a protein vector that delivers engineered proteins of interest to the brain after peripheral administration.
“The parasite’s ability to pass through the BBB and communicate with the neurons, combined with our ability to engineer the parasite, generate a golden opportunity for solving the great therapeutic challenge of delivering medications to the brain,” said Lilach Sheiner, toxoplasma expert from the University of Glasgow in Scotland.