Parasites wreak havoc on human and veterinary health, but researchers may have found a way for patients with brain disorders and a common brain parasite to become friends and foes.
New research published in Nature Microbiology has pioneered the use of a single-celled parasite. Toxoplasma gondiito inject therapeutic proteins into brain cells. The brain is very selective about what it takes in, including many drugs, which limits treatment options for neurological conditions.
As a professor of microbiology, I have dedicated my career to finding ways to kill dangerous parasites. ToxoplasmaThe possibility that they could use their weapons to treat other diseases fascinates me.
Microbes as medicine
Ever since scientists realized that microscopic organisms could cause disease—the 19th-century germ theory of disease—humanity has sought to keep infectious agents out of our bodies. Many people’s understandable aversion to microbes may make the idea of adapting these microbial enemies for therapeutic purposes seem counterintuitive.
But the history of preventing and treating disease by incorporating the microbes that threaten us dates back long before germ theory. In the early 1500s, people in the Middle East and Asia noticed that those lucky enough to survive smallpox never got infected again. These observations led to the practice of deliberately exposing an uninfected person to material from an infected person’s pus-filled wounds—which, unbeknownst to them, contained weakened smallpox virus—to protect them from serious illness.
The concept of vaccination has led to the emergence of numerous vaccines that have saved countless lives.
Viruses, bacteria, and parasites have also developed tricks up their sleeves to get into organs like the brain, and can be repurposed to deliver drugs to the body. Such uses could include viruses for gene therapy and gut bacteria to treat a type of intestinal infection known as enteritis. C. different.
Why don’t we just use pills for brain diseases?
Pills provide a convenient and effective way to get medicine into your body. Chemical drugs like aspirin or penicillin are small and easily absorbed from the gut into the bloodstream.
On the other hand, biologic drugs such as insulin or semaglutide are large, complex molecules that are susceptible to being broken down in the stomach before they can be absorbed, and they are too large to pass through the intestinal wall into the bloodstream.
All drugs, especially biologics, have great difficulty penetrating the brain because of the blood-brain barrier, a layer of cells lining the brain’s blood vessels that acts like a gatekeeper to prevent germs and other unwanted substances from reaching neurons.
Toxoplasma offers delivery service to brain cells
Toxoplasma The parasites infect all animals, including humans. Infection can occur through multiple routes, such as ingesting spores released in the feces of infected cats or consuming contaminated meat or water. In otherwise healthy individuals, toxoplasmosis produces only mild symptoms, but can be serious in people with weakened immune systems and in pregnant fetuses.
Unlike most pathogens, Toxoplasma can cross the blood-brain barrier and invade brain cells. Once inside neurons, the parasite secretes a series of proteins that alter gene expression in its host, and this may be a factor in the behavioral changes it causes in infected animals and humans.
In a new study, a global team of researchers took over the system Toxoplasma to secrete proteins into the host cell. The team genetically engineered Toxoplasma Combining one of their secreted proteins with a protein called MeCP2, which regulates gene activity in the brain, to make a hybrid protein — essentially, giving MeCP2 a backpack ride to neurons. The researchers found that the parasites secreted the MeCP2 protein hybrid into neurons grown in a petri dish and into the brains of infected mice.
A genetic deficiency in MECP2 causes a rare brain development disorder called Rett syndrome. Gene therapy trials are underway using viruses to deliver the MeCP2 protein to treat Rett syndrome. Toxoplasma It could deliver a form of the MeCP2 protein into brain cells, providing another option to treat this currently untreatable condition and could also offer another treatment option for other neurological problems caused by faulty proteins, such as Alzheimer’s and Parkinson’s disease.
We have a long road ahead of us
The path from the lab bench to the end of the bed is long and full of obstacles, so don’t expect to see anything engineered. Toxoplasma I will come to the clinic soon.
Obvious complexity in use Toxoplasma for medical purposes, it can cause a serious, lifelong infection that is currently incurable. Infecting someone Toxoplasma can damage critical organ systems such as the brain, eyes and heart.
However, one third of people worldwide are currently Toxoplasma in their brains, apparently without incident. Emerging studies have linked the infection to an increased risk of schizophrenia, anger disorders, and recklessness, and hinted that this silent infection may predispose some people to serious neurological problems.
Widespread prevalence Toxoplasma infections can also be another complication, disqualifying many people from using it for treatment. Since billions of people who already carry the parasite have developed immunity against future infections, therapeutic forms Toxoplasma Once injected, they would be quickly destroyed by their immune systems.
In some cases, the benefits of using Toxoplasma as a drug delivery system, its benefits may outweigh the risks. Engineering benign forms of this parasite could produce the proteins patients need without harming the organ that defines who we are: the brain.
This article is republished from The Conversation, a nonprofit, independent news organization that brings you facts and trusted analysis to help you understand our complex world. By Bill Sullivan Indiana University
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Bill Sullivan receives funding from the National Institutes of Health.