Toxoplasma gondii tissue cyst in mouse brain (Wikipedia)
In a groundbreaking collaboration, researchers from Tel Aviv and Glasgow Universities have genetically modified the ‘cat parasite’ Toxoplasma gondii to transport medications directly to the human brain.
The study was led by Prof. Oded Rechavi from the Department of Neurobiology and the Sagol School of Neuroscience at Tel Aviv University, together with his PhD student Dr. Shahar Bracha, and with Prof. Lilach Sheiner, an Israeli scientist and toxoplasma expert from the University of Glasgow in Scotland. The results were published in the leading scientific journal Nature Microbiology.
Toxoplasma gondii is a single-celled parasite primarily known for causing toxoplasmosis, an infection that can affect humans and animals. While typically associated with mild or no symptoms in healthy individuals, it can be severe for pregnant women and people with weakened immune systems.
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The recent breakthrough research, however, has unveiled a surprising potential for this parasite. Scientists have managed to harness its unique biological properties to transform it into a carrier for delivering drugs directly to the human brain. This innovative approach opens up new possibilities for treating neurological diseases.
“One of the biggest challenges in treating neurological diseases is getting through the blood-brain barrier (BBB),” explains Prof. Rechavi. “It is very difficult to deliver drugs to the brain via the blood stream, and this is especially true for large molecules such as proteins, the critical ‘machines’ that carry out many important functions inside the cell.”
The creative solution proposed by the TAU team utilizes the unicellular parasite Toxoplasma gondii, which can infect a vast variety of organisms, but reproduces only in the guts of cats. The parasite is very effective in infecting humans, with an estimated third of the global population infected at some point in their lives. Prof. Rechavi explains: “Most people don’t even feel the infection or only experience mild flu-like symptoms. 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, that 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.”
The parasite’s ability to penetrate the human brain and survive there in a dormant state, without reproducing, made it a perfect candidate for the researchers’ novel approach: genetically engineering Toxoplasma gondii to secrete therapeutic proteins.
This groundbreaking research holds immense promise for treating a wide range of debilitating diseases. In this study, the team successfully demonstrated the use of engineered Toxoplasma gondii to deliver MeCP2, a protein crucial for brain function, to target cells. “Rett syndrome, a fatal condition caused by a lack of MeCP2 in brain cells, is a prime example of a disease that could potentially benefit from this new approach,” explains Professor Rechavi. “However, this is just the tip of the iceberg. Numerous other diseases are linked to protein deficiencies or imbalances.” To expedite the development of safe and effective treatments based on this technology, the researchers have co-founded Epeius in partnership with Tel Aviv University’s Ramot and the University of Glasgow.
