University scientists find unlikely HIV cure in anti-fungal foot cream
A new study conducted by Rutgers scientists shows the cure for the human immunodeficiency virus may come from an unexpected source.
In a preclinical study conducted at the New Jersey Medical School, now a branch of Rutgers Biomedical and Health Sciences, researchers have found that ciclopirox, an active ingredient in anti-fungal foot cream, completely eliminates HIV in human cell cultures.
Michael Mathews, head of the research team, said current anti-HIV drugs only inhibit the virus from spreading to other cells. Once a patient stops using these drugs, HIV often comes back.
Mathews, a professor of biochemistry and molecular biology at Rutgers-Newark, said the drugs’ effectiveness is limited. Development of mutations from HIV resistant to the drugs is always an issue.
But ciclopirox avoids the issue of resistance completely. The team’s most recent work, published in the scientific journal PLOS ONE, reveals ciclopirox produces no rebound of the virus in the cell cultures.
“It’s the first time we’re seeing the prospect of killing HIV,” he said.
Mathews said ciclopirox inhibits HIV’s ability to disable cells’ altruistic suicide pathway, by which infected cells normally kill themselves to prevent spread of the infection. It does this by inhibiting the protein hydroxylase, which has long been associated with proliferation of HIV.
The team performed successful experiments on real and synthetic human cell cultures. Though his team has not completed clinical trials yet, Mathews said preclinical results are promising.
“It’s a new chapter in the fight against HIV and AIDS,” he said.
In an interview with Drug Discovery & Development magazine, Mathews said the team’s peers did not feel the same way.
“To my knowledge no one else has advanced the idea. … We can be pretty sure of this because of the stiff opposition we experienced during the review process at other journals,” he said.
In the same interview, Dr. Robert Gallo, the co-discoverer of HIV, said he is unsure of the research’s significance.
“I haven’t seen any results where they isolate [ciclopirox] and show it can be used systemically,” said Gallo, a professor at the University of Maryland School of Medicine.
Mathews told The Daily Targum he disagrees. Although ciclopirox is a topical medicine, he said it is possible to transform it into a pill or injection since the Food and Drug Administration has already approved the drug for human use.
He said his research team has already performed successful experiments administering ciclopirox via stomach absorption on animals.
Still, Mathews stressed the importance of conducting clinical trials.
“It’s in [the virus’s] name. It’s a human virus,” he said.
Now, Mathews said it is only an issue of time and funding. Theoretically, trials could begin in less than one year.
“We’re excited, but it’s hard to tell when we’ll get approval,” he said.
For now, the team has been working with deferiprone, another FDA-approved drug that has the same effect on HIV-infected cells as ciclopirox.
Matthews said deferiprone treats thalassemia, a disease that weakens and destroys red blood cells in the body. Unlike ciclopirox, the FDA has approved deferiprone for systemic use.
He said clinical trials involving deferiprone have already begun in South Africa. They have shown deferiprone works against HIV both in vitro and in vivo.
Mathews said the team skipped animal trials, showcasing a model for rapid development of drugs in a petri dish into forms consumable for patients.
The team’s work is only at its first stage. Co-author Dr. Hartmut Hanauske-Abel said the research team has only conceived a concept on how to terminate HIV.
“We have not made any impact on the pandemic,” said Hanauske-Abel, an assistant adjunct professor at NJMS. “We merely published cell culture findings.”
The Centers for Disease Control and Prevention estimate 1,148,200 people over the age of 13 in the United States are living with HIV infection. About 50,000 new incidences of infection occur every year.
“Everyone who has HIV dies from HIV — [we have] no cure,” Hanauske-Abel said.
He told Drug Discovery & Development that he sees the potential in the study’s findings.
“All told … the approach may offer hope that a cure for HIV may be no farther away than the local pharmacy,” he said.
In response to Gallo, he said the team’s preclinical work and other studies have indicated ciclopirox may work systemically before and after infection, just like deferiprone does.
But Hanauske-Abel said the systemic tests have focused on another major disease — cancer.
He told Drug Discovery & Development a research group at the University of Toronto isolated ciclopirox and used it systemically with some success against a form of leukemia.
He also said a Louisiana State University group showed the drug rids cells of tumors using the same mechanism to rid cells of the HIV virus.
“The [PLOS ONE] paper suggests we change dogma,” Hanausuke-Abel said.
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