Brain parasite could be used to treat neurological diseases

BY ANTHONY KING

A parasite can ferry therapeutic proteins to brain cells, an international collaboration has demonstrated. A team at the University of Glasgow, UK, engineered the parasite, Toxoplasma gondii, so that it would deliver large proteins to human neurons (Nature Microbiology, DOI: 10.1038/s41564-024-01750-6).

The protozoan parasite reproduces in cats and infects many kinds of mammals and birds. It has a natural ability to travel from the human gut to the central nervous system: an estimated one-third of people have T. gondii cysts in their brain. The researchers wanted to see whether – with some key changes – this parasite could be used to safely deliver therapeutic proteins that could help treat neurological diseases.

It is currently difficult for modern medicine to land genes or proteins into the brain.

‘There’s been decades of research trying to deliver therapies into the brain using viral therapy, nanoparticles and other ways,’ says Lilach Sheiner, who heads up the Glasgow lab involved in the new research. ‘We decided to piggyback on the innate ability of toxoplasma to cross the blood brain barrier and then spit proteins into neurons.’

This was demonstrated by using the parasite to deliver a protein, MeCP2, which has already been proposed as a promising therapeutic target for Rett syndrome.

The toxoplasma parasite was used to transport proteins into neurons in a dish, into brain organoids in the lab and into mice by labs in Arizona, Israel, Italy and Glasgow, UK.

‘We achieved a proof-of-principle in having the parasite make the therapeutic proteins, even though these are proteins from mammals,’ says Sheiner. She notes, however, that it is far from patients right now, estimating five to 10 years.

She adds: ‘It’s really important to remember that these are pathogens and can kill people with immune deficiencies.’ The Glasgow group is working with Israeli biotech Epeius Pharma to weaken the parasite and render it safer.

‘We’re stuck with viruses, mostly adeno-associated virus (AAV) 9, as a way of delivering genes that would express proteins for gene therapy or for gene editing,’ says Adrian Bird, a geneticist at the University of Edinburgh, UK, who led the research into a therapeutic protein for Rett syndrome by showing its effectiveness in mice.

‘But AAV9 doesn’t infect that many nerve cells, so you struggle to deliver enough, and it has a limited capacity.’ The idea of hijacking a parasite as a delivery vehicle, says Bird, is ‘exciting and interesting, but whether it pans out is a little bit uncertain. More needs to be done.’