Protein found to cross blood-brain barrier

My research group has been very interested in understanding how a fungal pathogen causes a brain infection and why is this important
and why do we care about it? Well, the organism we work with, called Cryptococcus neoformans, is the leading cause of fungal meningitis worldwide. So, there are about a million cases or so a year and about 650,000 deaths. And it’s a devastating disease, and we’re very
interested in understanding the mechanism of how it is able to cross the blood-brain
barrier and then get into the brain. So, in general, we’ve got a protective membrane that surrounds the brain called the blood-brain barrier. And usually it does a very good job
of keeping harmful chemicals, toxins and so on out of our brain, but in this case, with
this specific pathogen, this fungus that we work with, it has managed to breach the blood-brain barrier and get into the brain. So, in our studies we’ve been trying to identify proteins within the pathogen that it is using to help it get across the blood-brain barrier. And
so in doing so we identified a new protein. It’s a metalloprotease that essentially chews up other proteins. We found that if we knockout the gene that encodes the protein, we found that this pathogen no longer crosses the blood-brain barrier. And we demonstrated that both in
our in vitro model of the human blood-brain barrier and also in vivo looking at mice.
And it’s very clear in our studies that in the absence of this metalloprotease, there
was a complete lack of the pathogen in the brain. So that suggests that this protein
plays an important role, a key role, in helping this fungus get across the blood-brain barrier. The fact that we’ve identified a protein that is crucial to the development of this fungal
meningitis suggests that it could be a good drug target. And there are a few antifungal
drugs out there, but many of them are quite toxic, and really the repertoire of drugs
available to patients suffering from fungal meningitis are very few. So if we can identify a new protein perhaps like this metalloprotease as a means to develop better antifungals,
that’s a great thing. And secondly, the results showing that when we expressed this protein in this nonpathogen yeast and suddenly we could get it to cross suggests something very interesting and potentially hugely important in that we are proposing that possibly we
could take this protein, attach it to some kind of nanocarrier and use that to develop
a platform technology for the delivery of drugs into the brain, not only for the treatment of infections but importantly things like brain cancer and neurodegenerative diseases. As you know, when you’re trying to treat these types of terrible diseases, the main obstacle is the blood-brain barrier. Most drugs, most therapeutic drugs, can’t get into the brain
because of the barrier. So, if we could then take this metalloprotease, which we’ve shown can penetrate the blood-brain barrier, then presumably we might be able to attach it to
some kind of nanocarrier that is loaded with an important therapeutic drug and then potentially you can get it into the brain for the treatment of these neurodegenerative and other disorders.

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