Bioengineered parasites could one day deliver drugs to your brain

Intentionally infecting yourself with the Toxoplasma gondii parasite is not a recommended medical procedure. Although most people do not develop noticeable symptoms, a smaller proportion of hosts inevitably suffer from toxoplasmosis each year – a condition that can bring weeks of flu-like symptoms, muscle aches and swollen lymph nodes.

T. gondii controls this by successfully traveling from the intestines through the blood-brain barrier (BBB), a vital biological function that protects the central nervous system from unwanted foreign molecules. And while the parasite has no problem crossing the BBB, potentially life-saving drugs that can cross that threshold remain difficult to develop. But what if those drugs hitch a ride on a genetically modified version of the parasitic protozoa?

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That’s a possibility being explored by an international team of neurobiologists who detailed their latest work in a study published July 29 in the journal Natural microbiology. According to them, it could one day be possible to turn parasites into harmless chemical payload carriers used to treat neurological problems.

To demonstrate an early version of the concept, neurobiologists bioengineered two of them T. gondiiThe three organelles secrete a protein that is often used in patients with Rett syndrome. The currently incurable genetic condition, documented in an estimated 1 in 8,500 newborns, affects almost exclusively women and results in lifelong physical and neurological problems.

After changing T. gondiiIn the organelles of the human brain, the team initially introduced the parasite into laboratory-grown human brain organoids, where it successfully delivered the MeCP2 protein to specific neurons. From there, they conducted three additional tests with mice: One group received a saline injection of the modified substance T. gondii, while the second set received the unchanged parasite. Meanwhile, another group served as a control with no exposure to artificial or natural samples. Even if changed, the T. gondii delivery parasites still managed to successfully cross the mouse blood-brain barrier and deliver MeCP2 proteins.

That said, from now on T. gondii remains T. gondii—with or without modified organelles. Regardless, the parasites can still cause toxoplasmosis. That said, these initial experiments were not intended to neutralize the parasite’s damage, but to show how their genetic design could potentially serve as a tool in medicine.

“The focus of this work is to provide a proof of concept for the feasibility of use T. gondii as versatile protein vectors, as well as preliminary guidelines for the future development of this approach,” the team wrote in their accompanying appendix research briefing, adding that the parasites currently still only provide relatively low levels of protein. Still, the team believes that further experimentation could one day solve these problems and potentially enable a new, effective alternative to navigating the notoriously difficult blood-brain barrier.