Parasite Could Revolutionize Brain Treatment Delivery
TEHRAN (Tasnim) – Scientists suggest that the parasite Toxoplasma gondii could be engineered to deliver therapeutic proteins to brain cells, potentially offering new treatments for hard-to-reach conditions.
A parasite capable of crossing the blood-brain barrier to infect brain tissue may one day deliver crucial therapeutics.
Toxoplasma gondii, which thrives in nearly all warm-blooded life, could be modified to deliver therapeutic proteins to brain cells, offering treatment options for challenging conditions.
The research, tested in lab-grown human brain tissue and living mice, showed minimal side effects, suggesting the concept is plausible and may have broader applications, such as studying the brain, with further research and tweaking.
"In this study, we show that T. gondii can be used to address many of the challenges associated with protein delivery for research and therapeutic applications," writes a team led by neuroscientist Shahar Bracha of the Massachusetts Institute of Technology.
"We demonstrate the use of T. gondii as a versatile delivery system in cultured fibroblasts, in vitro-differentiated neurons, primary neurons, human brain organoids, and in vivo in mice, and characterize factors that affect delivery patterns under different conditions."
The blood-brain barrier, a membrane separating blood vessels from brain tissue and the central nervous system, prevents most large and hydrophilic molecules, including therapeutic proteins, from entering the brain.
T. gondii has found ways to cross the blood-brain barrier. Although the protozoan causes toxoplasmosis, a condition with serious complications, Bracha and her colleagues wondered if its ability to cross the barrier could be harnessed for good.
Within the central nervous system, T. gondii primarily interacts with neurons, using three organelles to secrete substances. Researchers altered two of these organelles to secrete proteins known to treat human neurological conditions.
The engineered T. gondii was tested on several systems, including human brain organoids treated with T. gondii engineered to deliver MeCP2, a protein used to treat Rett syndrome, a rare genetic disorder affecting brain development.
In lab-grown tissues, the delivered protein bound to the DNA of the organoid and altered gene expression compared to controls exposed to unaltered T. gondii, suggesting successful delivery of the functional protein.
To test the system in living organisms, researchers infected mice with edited T. gondii microbes, control groups with non-edited microbes, and a group injected with saline.
The edited T. gondii efficiently infected hosts like the non-edited parasites, delivered MeCP2, and caused minimal inflammation compared to the saline control group.
It's believed that 25 to 30 percent of people worldwide harbor T. gondii, with most being asymptomatic. Given this benign infection rate, leveraging T. gondii for therapeutic delivery could offer significant benefits.
The researchers believe their results present a new approach for treating neurological conditions and a powerful research tool for investigating protein activity in neurons.
"Neurons are particularly difficult to target with existing methods," they write. "T. gondii's ability to robustly deliver intracellular proteins to neurons emphasizes its potential as a research tool."
