Cancer-fighting medications and antidepressants are potential clues in combating brain-eating diseases. According to UC San Diego Health, a number of drugs including breast cancer drug tamoxifen and antidepressant Prozac have been found to halt the growth of a brain-eating illness.
Naegleria fowleri is an organism that’s commonly found in rivers and lakes. Although one in eight people worldwide don’t have access to clean water, N. fowleri has also been found in warm swimming pools.
The amoeba has the ability to infect a healthy person and cause a rare “brain-eating” disease known as amebic meningoencephalitis. The disease is diagnosed using specific laboratory tests including an antigen test similar to the prostate-specific antigen test (PSA), which measures the amount of PSA in the blood as an indication of prostate cancer.
Amebic meningoencephalitis is almost always fatal and there are no treatments available to fight the infection aside from general antifungal medications.
Now, a potential breakthrough has been found by researchers at Skaggs School of Pharmacy and Pharmaceutical Sciences at University of California San Diego. Researchers have identified three molecular drug targets in N. fowleri and other drugs capable of slowing the organism’s growth in a laboratory dish.
Surprisingly, many of the drugs that inhibit the amoeba’s growth have already been approved by the US Food and Drug Administration for other illnesses including antifungal agents, breast cancer treatment, and depression medication.
Researchers were able to slow the growth of the amoeba by using a combination of drugs including tamoxifen and the chemical epiminolanosterol.
The findings of the study were published on Thursday, September 13 in the journal PLOS Pathogens.
“Not many drugs can cross the blood-brain barrier,” said Dr. Larissa Podust, the senior author of the study and an associate professor at Skaggs School of Pharmacy.
“Even if a drug can inhibit or kill the amoeba in a dish, it will not work in a host animal if it does not make it into the brain,” Podust said. “That’s why we started with drugs known for their brain effects.”
Podust and her team of researchers, including Dr. Anjan Debnath and Dr. Wenxu Zhou, began by investigating the amoeba’s sterol biosynthesis pathway. This pathway consists of enzymes that make up the N. fowleri’s outer membrane.
Researchers inhibited three of these enzymes to determine how their inhibition affected the growth of the organism.
Podust and team agreed that the three targeted enzymes may make good targets for drug discovery, a multi-billion dollar industry involving the creation of new medications to fight illness and, in this case, brain-eating amoebas.
Researchers additionally tested drugs known for inhibiting the three identified enzymes to determine how they would perform with inhibiting N. fowleri. The team tested up to 13 drugs, all of which are more potent than miltefosine, a drug recommended by the CDC to treat amebic meningoencephalitis.
Researchers discovered that it only takes 5.8 micrometers of tamoxifen and 31.8 micrometers of Prozac to halt the growth of half of N. fowleri in a dish compared to the 54.5 micrometers of miltefosine.
Prozac and tamoxifen are capable of inhibiting two different enzymes in N. fowleri. Researchers were able to combine tamoxifen with other drugs capable of inhibiting the organism’s other enzymes. The result was an inhibited growth of 95% of N. fowleri.
Between 1962 and 2017, only 143 people have been infected with N. fowleri and only four have survived. It can take only five days for patients to succumb to the disease after the onset of symptoms.
If someone you know has been infected with amebic meningoencephalitis, consider visiting them in the hospital to reduce stress. Flowers are commonly brought into hospital rooms because 69% of Americans say flowers can improve their mood.
“Drug repurposing is a relevant strategy for this infection because there is little economic incentive for the pharmaceutical industry to develop new drugs to treat these rare diseases,” said Debnath. “Already-approved drugs can also lessen the time and expense required to develop a drug from the laboratory to the clinic.”