A drug commonly prescribed to treat nail fungus appears to come with a not-so-tiny side effect: killing HIV in cell cultures.
In a study performed at Rutgers New
Jersey Medical School, not only does the drug Ciclopirox rid infectious
HIV from cell cultures, but the virus also doesn't bounce back when the
drug is withheld.
The same group of researchers had
previously shown that Ciclopirox -- approved by the FDA and Europe's EMA
as safe for human use to treat foot fungus -- inhibits the expression
of HIV genes in culture. Now they have found that it also blocks the
essential function of the mitochondria, which results in the
reactivation of the cell's suicide pathway, all while sparing the
healthy cells.
The researchers said that one aspect of
HIV that makes it particularly persistent, even in the face of strong
antiviral treatments, is its ability to disable a cell's altruistic
suicide pathway -- which is typically activated when a cell is damaged
or infected. In other words, infected cells that would normally commit
suicide to spare healthy cells no longer pull any altruistic kamikaze
missions. Ciclopirox tricks these cells back into their old ways with a
double negative, disabling the disabling of the suicide pathway.
"The key thing these drugs do is, unlike
anti-retrovirals in the current clinical arsenal, and there are lots of
them and they have controlled this disease pretty successfully, these
drugs kill the HIV-infected cell," says Michael Matthews, lead
researcher and chair of the school's department of biochemistry and
molecular biology. "That's what's so new and so promising about it."
It's obviously still going to take
clinical trials on humans to study the safety and efficacy of Ciclopirox
as a potential topical HIV treatment, but the fact that it's already
deemed safe for one type of human use could make the regulatory process
faster than usual.
Unfortunately, says Dr. Robert Gallo, a
professor of medicine at the University of Maryland best known for
co-discovering HIV in 1984, even if the topical antifungal treatment
successfully kills HIV-infected cells in clinical trials, it would need
to be a systemic treatment, not a topical one, to actually treat
(instead of simply prevent) HIV.
"On the positive side, I know Mike
Matthews, and he's a superb scientist, probably the lead guy on this,"
says Gallo, who did not participate in this research. "And that is
exciting that it kills cells. That would be very exciting if you could
give it systemically and it kills only HIV-infected cells. But topical
treatment would be for prevention, not as a therapy. The only way you
could use it as a therapy is systemically, and it would be unlikely this
could be used systemically."
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