Toxoplasmosis causing agents are produced in the brain
Toxoplasmosis is widespread. Yet, most people don't notice it. Researchers are exploring the parasite's ability to reach the brain. A feasibility study has shown promising results.
The Toxoplasma gondii parasite is known for invading the brains of mammals and birds. An international research team has now utilized this ability to cross the blood-brain barrier: In a feasibility test, they modified the parasite to produce a potentially therapeutic protein against a disease and deliver it into brain cells. However, the effectiveness and safety of this entirely new approach still need to be demonstrated and improved, writes the group led by Shahar Bracha from Tel Aviv University in the journal "Nature Microbiology".
So far, delivering proteins to the brain has proven extremely challenging due to various reasons, the team writes. These substances are often too large to cross the blood-brain barrier, are unstable, and can trigger immune reactions. If there were a way to specifically deliver proteins to the brain, it would open up many possibilities, not only for therapies but also for studying fundamental processes.
This is where the Toxoplasma gondii parasite comes into play, which is widespread worldwide and has infected an estimated 50% of the population in Germany, usually without causing symptoms. The parasite, which exists in different strains, is typically ingested orally, crosses the blood-brain barrier, and can invade brain cells, where it can reside for life.
Protein production and feasibility
The single-celled organism uses three different organelles to produce proteins - micronemes, rhoptries, and dense granules. The study, involving researchers from the US, UK, Italy, and Switzerland, demonstrates that the latter two can be used to specifically produce and deliver proteins into the host's brain cells.
The team tested this particularly with the protein MeCP2, which is thought to alleviate symptoms of Rett syndrome, a hereditary developmental disorder. After various laboratory tests, the team injected genetically modified T. gondii parasites that can produce this protein into the abdominal cavity of mice. The animals were then killed and examined after one month or three months. Most parasites were found to have settled in the brain, with no noticeable inflammatory reactions observed.
Parasite delivers proteins to multiple cells
Rhoptries appear to offer the advantage that the parasite does not have to be in a single cell, but can inject the protein into different cells, the group writes. Dense granules, on the other hand, could produce larger amounts of the protein and do so over longer periods, they add: "Due to their respective advantages, these systems could be suitable for different types of protein delivery measures."
The researchers emphasize that it is particularly important to weaken the parasite, pointing to viral gene therapies or microbiome therapies. "Although natural infections in immunocompetent individuals are typically asymptomatic, T. gondii can have detrimental effects in a variety of situations," they note. Now, the focus is on optimizing the efficiency and safety of this approach.
Martin Blume of the Robert Koch Institute (RKI) notes that there have been discussions for some time about using Toxoplasma organisms therapeutically, for instance in cancer medicine. In the study, the production of specific proteins in the brains of mice seemed to work. However, it remains unclear in which of its various developmental stages the pathogen produces the protein. Furthermore, the MeCP2 concentrations are uncertain, emphasizes the Toxoplasma expert. Generally, there are doubts about applying the parasite to humans, especially because the details of Toxoplasma infections in the human brain are still not well understood.
The use of Toxoplasma gondii as a delivery vehicle for therapeutic proteins could revolutionize brain-related treatments, highlighting the potential impact of education in this field. This groundbreaking approach could lead to advancements in not only therapies but also our understanding of fundamental brain processes, underscoring the importance of continued research in this area.
The potential application of Toxoplasma gondii in medical therapy is a topic of ongoing discussion, with some exploring its use in cancer treatment. If successful, this could be a significant breakthrough, emphasizing the need for further education and exploration in this area to minimize risks and maximize benefits.
