- A parasite that is most widely known for its existence in cat feces could be a delivery system for proteins that target neurological disorders, a new study has found.
- Researchers successfully targeted protein dispersal by using an engineered version of Toxoplasma gondii, a parasite in cat feces and undercooked meat that is largely harmless to humans.
- Experts say such methods are not new and that this one will require more research, but that it does hold promise.
The parasite infamous for its existence in cat feces can be effectively used as a delivery system to ferry therapeutic proteins to neurons in the brain, a new study published in Nature Microbiologyshows, suggesting that a number of neurological disorders could be treated this way.
Toxoplasma gondii, which notoriously is associated with a danger to pregnant women and people with compromised immune systems, infects about one-third of the global population.
It can be contracted by eating undercooked meat, and it reproduces in the guts of cats. It can remain in a host’s brain for their entire life. Most people who are infected will have no serious side effects or health issues.
The lead researchers were based at the Department of Neurobiology and the Sagol School of Neuroscience at Tel Aviv University, and the University of Glasgow in Scotland.
Taking advantage of the parasite’s usual ability to secrete proteins, the researchers genetically engineered the parasite to be able to deliver therapeutic proteins once it had crossed the blood-brain barrier, which has generally been an obstacle for such treatments.
In the current study, researchers injected genetically altered parasites into mice to deliver proteins into cell nuclei. They identified three basic methods that the parasite uses to secrete proteins and found that their engineered version could use two of those simultaneously.
The researchers also found that this delivery system’s was able to secrete MePC2, a protein whose deficiency is associated with Rett syndrome, a neurological disorder that mainly affects women. This suggests greater potential for targeting other neurological disorders using the parasite.
“T. gondii’s ability to robustly deliver intracellular proteins to neurons emphasizes its potential as a research tool,” the study authors write. “Neurons are particularly difficult to target with existing methods, as they are less receptive to uptake of transfection reagents and to expression of exogenously delivered DNA.”
Jasmin Dao, MD, PhD, a pediatric neurologist at Miller Children’s & Women’s Hospital Long Beach in California, who was not involved in the study, told Medical News Today that most human responses to T. gondii are generally quite mild, but once it finds a host it has extremely robust methods of furthering its survival.
“Most people infected with T. gondii are asymptomatic or display mild flulike symptoms, such as muscle aches, fatigue, or fevers. In those with weakened immune system, more severe neurologic symptoms can occur such as seizures or encephalitis,” Dao said.
She further explained that:
“T. gondii survives in human hosts by reducing host cells immune responses and enhancing parasite proliferation. It can hijack host cell machinery allowing for host cells infected with parasite to thrive and replicate, as well as initiate autophagy of healthy host cells so there are fewer healthy cells to attack the infection.”
Because T. gondii can latch itself to humans’ central nervous systems so effectively without significant damage to its hosts, researchers saw an opportunity to create specific targeting of certain proteins “with known utility in neurons,” the study says.
The parasite’s three different organelles for protein secretion seemed to indicate a strong chance that such targeting could be successful.
Dao told us that the study’s results highlight the great potential for targeting other neurological disorders.
“Our brain protects itself by through a protective layer called the blood-brain barrier. This helps the brain hold onto things that are helpful and keeps harmful things out, such as toxins or infections. Because of the tight regulation of the blood-brain barrier, it can be very difficult to get drugs directly to the brain to combat neurologic disorders,” she explained.
“Using T. gondii to inject therapeutic proteins into brain cells presents a novel potential approach to treating neurologic disorder conditions caused by specific protein deficiencies, such as Fragile X or Duchenne Muscular Dystrophy,” Dao added.
Dao acknowledged that there can be risks using parasitic organisms like T. gondii for medical purposes.
“In those with weakened immunity there may be potential risk of developing serious heart, brain, or eye infections,” Dao said. “Recent studies show that T. gondii infection is also associated with behavioral, psychiatric, and personality alterations, as well as increased risked of schizophrenia.”
Santosh Kesari, MD, PhD, a board-certified neurologist at Pacific Neuroscience Institute in Santa Monica, CA, and Regional Medical Director for the Research Clinical Institute of Providence Southern California, who was not involved in the study, said that similar techniques have been used for decades, but that this particular one was still in the early stages of research.
“Scientists have been using various microorganisms from viruses to bacteria for treatment of patients with various diseases in the past century. Only a few modified agents are FDA [Food and Drug Administration] approved — such as herpes virus for melanoma and adenovirus for bladder cancer — and many others are in clinical development.”
– Santosh Kesari, MD, PhD
“This is [research in the] early stage, and will take many years to optimize the best engineered parasite for a particular use and to understand the delivery and safety challenges in larger animals and primates before clinical trials in humans,“ he noted.
According to Kesari: “One concern is the parasite going awry and causing side effects in humans from inflammation, infection including encephalitis. The scientists will have to engineer the parasite with many safety features to get rid of it whenever needed.”
