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Researchers from Tel Aviv University (TAU) recently discovered a method to deliver neurological treatment to the human brain using an engineered version of Toxoplasma gondii, commonly known as “the cat parasite.”

One of the biggest challenges in treating neurological diseases is getting the therapeutic drugs through the blood-brain barrier (BBB).

“It is very difficult to deliver drugs to the brain via the bloodstream; this is especially true for large molecules such as proteins, the critical ‘machines’ that carry out many important functions inside the cell,” said Prof. Oded Rechavi from TAU’s Department of Neurobiology and Sagol School of Neuroscience, who led the study.

The study was conducted in collaboration with Rechavi’s PhD student Shahar Bracha, and Prof. Lilach Sheiner, an Israeli scientist and toxoplasma expert from The University of Glasgow.

The findings were recently published in the scientific journal Nature Microbiology.

Cat parasite

To solve the BBB problem, the research team utilized Toxoplasma gondii, which can infect a vast variety of organisms, including humans, but reproduces only in the guts of cats.

It is estimated that a third of the global population is infected by the parasite at some point in their lives. “Most people don’t even feel the infection or only experience mild flu-like symptoms,” added Rechavi. 

What made the parasite the perfect candidate for the novel study is its ability to penetrate the human brain and survive there in a dormant state, without reproducing. This prompted the team to genetically engineer Toxoplasma gondii to secrete therapeutic proteins.

“The parasite has three distinct secretion systems,” explained Rechavi.

“One of the systems ‘shoots’ a ‘harpoon’ into the neuron, to enable penetration. Once inside, the parasite forms a kind of cyst in which it continues to secrete proteins permanently. We engineered the parasite’s DNA to make it produce and secrete the proteins we want, which have therapeutic potential.”

The methodology

As part of the study, the team injected transgenic model animals with the genetically engineered parasite to produce and secrete proteins that travel into cell nuclei. Transgenic animals normally have a foreign gene deliberately inserted into their genome.

The scientists then gathered enough evidence to prove that the proteins had been delivered to the target area and remained active in the neurons’ nuclei.

The current study focused primarily on a protein called MeCP2, whose deficiency is associated with Rett syndrome, a rare neurological disorder that affects the way the brain develops.

Researchers emphasized, however, that the method could prove useful in the treatment of a series of diseases caused by deficiency or abnormal expression of a certain protein.

To ensure the method’s safe and effective therapeutic implementation, for both drug delivery and genetic editing, a company named Epeius Pharma, was established in collaboration with Ramot, the technology transfer company of Tel Aviv University, and with the University of Glasgow’s research and innovation services.

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