by Parasites have a huge impact on human and veterinary health. But researchers may have found a way for patients with brain disorders and a common brain parasite to become frenemies.
A new study published in Nature Microbiology has pioneered the use of a single-celled parasite, Toxoplasma gondii, injecting therapeutic proteins into brain cells. The brain is very picky about what it lets 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 such as Toxoplasma. The prospect of us being able to use their weapon instead to treat other galls intrigues me.
Microbes as medicine
Ever since scientists realized that microscopic organisms can cause illness – what became known as the 19th century germ theory of disease – mankind has been on a quest to keep infectious agents out of our bodies. Adapting these microbial attacks to germs for therapeutic purposes may seem counterintuitive to many.
But there is a history long before the germ theory of preventing and treating disease by co-opting the microbes that threaten us. As early as the 1500s, people in the Middle East and Asia noticed that those who were lucky enough to survive the infection never recovered. These observations led to the practice of deliberately not exposing a person to infections from pus-filled sores – unknowingly carrying the weak smallpox virus – to protect them from serious disease.
This inoculation concept has resulted in a plethora of vaccines that have saved countless lives.
Viruses, bacteria and parasites have also developed many tricks to affect organs such as the brain and could be manipulated to deliver drugs into the body. It may include viruses for gene therapy and intestinal bacteria to treat a known intestinal infection C. diff.
Why can’t we take a pill for brain disease?
Pills offer a convenient and effective way to get medicine into the body. Chemical drugs like aspirin or penicillin are small and easily absorbed from the gut into the bloodstream.
On the other hand, biological drugs such as insulin or semaglutide are large, complex molecules that are vulnerable to being broken down in the stomach before they can be absorbed. They are also too large to pass through the intestinal wall into the bloodstream.
All drugs, especially biologics, have great difficulty getting into the brain because of the blood-brain barrier. The blood-brain barrier is a layer of cells lining the brain’s blood vessels that act like a gatekeeper to prevent germs and other unwanted substances from gaining access to neurons.
Toxoplasma it sends a delivery service to brain cells
Toxoplasma parasites infect all animals, including humans. Infection can occur in a number of ways, including ingesting spores shed in the stool of an infected cat or consuming contaminated meat or water. Toxoplasmosis in otherwise healthy people produces only mild symptoms but can be serious in immunocompromised people and the pregnant fetus.
Unlike most pathogens, Toxoplasma it can cross the blood-brain barrier and invade brain cells. Once inside neurons, the parasite releases a series of proteins that alter gene expression in its host, which may be a factor in the behavioral changes it causes in infected animals and humans.
In a new study, a global team of researchers captured the system Toxoplasma used to secrete proteins into the host cell. The team did genetic engineering Toxoplasma to make a hybrid protein, fusing one of its secreted proteins with a protein called MeCP2, which regulates gene activity in the brain – in effect, giving MeCP2 a piggyback ride into neurons. Researchers found that the parasites inserted the MeCP2 protein hybrid into neurons grown in a Petri dish and in the brains of infected mice.
A genetic deficiency in MECP2 causes a rare brain development disorder called Rett syndrome. Gene therapy trials are using viruses to deliver the MeCP2 protein to treat Rett syndrome. Two Toxoplasma able to deliver a form of the MeCP2 protein into brain cells, may provide another option for treating this incurable condition. It may also offer another treatment option for other neurological problems caused by abnormal proteins, such as Alzheimer’s and Parkinson’s disease.
The long road ahead
The road from lab bench to bedside is long and full of obstacles, so don’t expect engineering Toxoplasma in the clinic anytime soon.
The clear complication in use Toxoplasma for medical purposes is that it can produce a serious life-long infection that is currently incurable. Infecting someone with Toxoplasma damage to critical organ systems, including the brain, eyes and heart.
However, up to a third of the people in the world currently carry Toxoplasma in their brains, apparently without incident. Emerging studies have correlated it with an increased risk of schizophrenia, rage disorder and recklessness, suggesting that this silent infection may be predisposing some people to serious neurological problems.
The widespread prevalence of Toxoplasma infections can also be another hassle, as it disqualifies many people from using it for treatment. Since the billions of people who carry the parasite have already developed immunity against future infection, therapeutic forms of Toxoplasma they would be quickly destroyed by their immune systems when depleted.
In some cases, the benefits of using Toxoplasma because a drug delivery system could overcome the risks. Engineering benign forms of this parasite could produce the proteins patients need without harming the organ – the brain – that defines who we are.
This article is republished from The Conversation, a non-profit, independent news organization that brings you reliable facts and analysis to help you make sense of our complex world. Written by: Bill Sullivan, Indiana University
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Bill Sullivan receives funding from the National Institutes of Health.
