Parasites that can cross the blood-brain barrier and infect the host’s brain may one day offer a means to deliver important therapeutic drugs.
Toxoplasma – One Parasites This protein, which is found in nearly every warm-blooded organism on Earth, could potentially be engineered to deliver therapeutic proteins to cells in the brain, providing a treatment option for hard-to-access diseases.
The research has been tested in lab-grown human brain tissue and in live mice with minimal side effects, proving that the concept is valid and that, with further research and fine-tuning, it could have broader applications, such as in brain research.
“In this study, Toxoplasma It can be used to address many of the challenges associated with protein delivery in research and therapeutic applications.” Write a team The study was led by Shahar Bracha, a neuroscientist at the Massachusetts Institute of Technology.
“we, Toxoplasma As a versatile delivery system in cultured fibroblasts, in vitro differentiated neurons, primary neurons, and the human brain Organoids We will conduct experiments in mice to characterize the factors that influence parturition patterns under different conditions.”
of Blood-brain barrierAs the name suggests, it is a membrane that separates blood vessels from brain tissue and the central nervous system, preventing harmful substances from the former from entering the latter.
This is a good thing overall, but the impermeability of the barrier Hydrophilic Large molecules block the entry of nearly all proteins, creating a major challenge for the delivery of therapeutic proteins that could help treat brain diseases.
Toxoplasma It is a parasite, Crosses the blood-brain barrierThat in itself is not good for humans or other animals.
This protozoan causes a disease called toxoplasmosis. Accompanied by unpleasant symptoms and rather serious complicationsBut Blaha and her colleagues wondered. T. gondiiCould the ability to cross the blood-brain barrier be harnessed for good?
In the central nervous system, Toxoplasma They are found primarily in neurons, interact with neurons, and form three separate Cell Organelles The researchers targeted two of these organelles, modifying them to secrete proteins known to treat neurological disorders in humans.
To test whether it would work, they engineered Toxoplasma In several types of systems, lab-grown chunks of human brain tissue called organoids Toxoplasma It is designed to deliver MeCP2, a protein used to treat a rare genetic disease. Rett SyndromeIt affects brain development and in most cases, MECP2 gene mutations.
In these laboratory-grown tissues, the delivered proteins Organoidsand alters gene expression compared to unmodified controls. ToxoplasmaThe results were interpreted by the researchers as successful delivery of functional proteins.
To see how it worked in vivo, the researchers infected mice with the edited genes. Toxoplasma a control group containing unedited microbes and mice injected with saline only.
Edited Toxoplasma They infected the host as efficiently as unedited parasites, but also delivered MeCP2 and caused minimal inflammation compared to saline controls.
about 25 to 30 percent A port for people all over the world Toxoplasmaand most are asymptomatic, so infections are generally benign. Either way, if it’s something we live with, there could be great benefits to be gained from using it to our advantage.
The researchers believe their findings not only open new avenues for treating neurological diseases, but also as a powerful research tool for investigating the activity of proteins within neurons.
“Neurons are particularly difficult to target using existing methods.” Those people write.Toxoplasma“The ability to potently deliver intracellular proteins to neurons highlights its potential as a research tool.”
This study Nature Microbiology.
