This innovative approach, detailed in a recent study published in Nature Microbiology, could revolutionize the treatment of neurological diseases such as Alzheimer’s, Parkinson’s, and Rett syndrome, which are often linked to protein dysfunction.
Toxoplasma gondii, a common parasite that resides dormant in approximately one-third of the global population, possesses the unique ability to cross biological barriers, including the formidable blood-brain barrier. This characteristic allows the parasite to infiltrate the brain and secrete proteins into neurons. The researchers believe that by harnessing and modifying this natural ability, Toxoplasma could be repurposed as an efficient delivery system for targeted therapies.
The study, co-led by Professor Lilach Sheiner from the University of Glasgow and Professor Oded Rechavi from Tel Aviv University, explored whether the parasite could be genetically engineered to produce and deliver therapeutic proteins directly to affected neurons. Their primary focus was on Rett syndrome, a severe neurological disorder caused by mutations in the MECP2 gene. The team engineered Toxoplasma to produce the MeCP2 protein, a promising candidate for treating Rett syndrome.
In lab tests using brain organoids and mouse models, the engineered Toxoplasma successfully delivered the MeCP2 protein to specific brain cells, demonstrating the feasibility of this novel approach. These early results indicate that the parasite can be manipulated to target precise locations within the brain, potentially offering a new way to treat neurological disorders that are otherwise difficult to manage due to the challenges of delivering therapeutics across the blood-brain barrier.
However, the researchers acknowledge significant challenges ahead. While Toxoplasma offers a promising delivery mechanism, its parasitic nature poses risks. To mitigate this, the team is working on engineering the parasite to self-destruct after delivering its therapeutic payload, ensuring that it does not cause further harm to the brain.
“This is very much a blue-sky project,” said Professor Sheiner. “Our collaborative team was thinking out of the box to try to tackle the long-standing medical challenge of finding a way to successfully deliver treatment to the brain for cognitive disorders.”
Sheiner also said that while the early results are promising, much more research and development are needed before this concept can be translated into a viable treatment option.
Professor Rechavi added: “Evolution already ‘invented’ organisms that can manipulate our brains; I think that instead of re-inventing the wheel we could learn from them and use
their abilities.” He suggests that leveraging the natural capabilities of Toxoplasma gondii could be a key step forward in developing effective treatments for neurological diseases.
The study, titled 'Engineering a Brain Parasite for Intracellular Delivery of Proteins to the Central Nervous System,' represents a pioneering step in the field of neurotherapeutics. While the road to clinical application may be long, this research opens new avenues for developing innovative treatments that could one day improve the lives of millions suffering from debilitating brain diseases.