School of Pharmacy Associate Professor Jennifer Golden and her collaborators are developing potential drugs for a severe brain infection caused by water contaminated with N. fowleri
On a hot summer day, there’s nothing more refreshing than a dip in a cool lake or a sprint through the sprinkler. And year-round, a nasal rinse with a Neti pot can bring sinus-clearing relief when suffering from a cold or allergies.
Unfortunately, the amoeba Naegleria fowleri can lurk in water sources, and when it enters the nose, it can cause a rare brain infection that is almost always fatal. Frequently dubbed in the media as “brain-eating amoeba,” reports of the infection typically emerge in the summer months, when the amoeba is most metabolically active and potential exposure increases as people engage in recreational water activities.
In August, an 8-year-old Louisiana girl — who is assumed to have contracted the amoeba while swimming near her lakeside home — died from primary amebic meningoencephalitis (PAM), the disease caused by N. fowleri, followed shortly by a North Carolina teen.
“We don’t have adequate drugs to address this infection, which is, in part, why the incidence of death associated with PAM is so high — about 97%.”
—Jennifer Golden
Jennifer Golden, an associate professor of pharmaceutical sciences in the University of Wisconsin–Madison School of Pharmacy and associate director of the School’s Medicinal Chemistry Center, was recently awarded a $3.8 million grant from the National Institutes of Health (NIH) to develop a targeted therapeutic for PAM. Golden is leading a multidisciplinary team with several long-term collaborators, including Clemson University geneticist and parasitologist James Morris, pharmacologist Bernd Meibohm from the University of Tennessee Health Science Center, and biochemist Ken Christensen from Brigham Young University.
This summer’s news headlines underscore the importance of the team’s work.
“We don’t have adequate drugs to address this infection, which is, in part, why the incidence of death associated with PAM is so high — about 97%,” says Golden. “We are working to fill that therapeutic gap.”
A rare but deadly infection
N. fowleri is located in soil, lakes, and streams worldwide; however, being exposed doesn’t guarantee an infection, Golden notes. The United States has had only 180 known cases between 1937 and 2025, according to the U.S. Centers for Disease Control and Prevention (CDC). Nonetheless, these statistics provide little consolation to families who are affected by N. fowleri. About 80% of reported cases involve children under age 18.
Current treatments for PAM include a combination of repurposed antibiotics, antifungals, and anticancer drugs that weren’t specifically designed or optimized to fight N. fowleri. Treatment is often delayed by misdiagnosis, thereby worsening outcomes.
“An infected person might experience a fever, a headache, or feel lethargic — symptoms that mimic more common infections such as meningitis,” Golden says. “By the time the correct diagnosis is made, critical time has passed. At that point, this amoeba has taken up residence in the brain and is causing catastrophic damage.”
Within a week or so of infection, N. fowleri can cause seizures, coma, or death. The bleak outcomes fuel Golden’s desire to find a better treatment for this devastating disease.
“Our goal is to develop an oral drug that is more efficacious and safer than drug cocktails that are currently used,” she says.
Pursuing a serendipitous discovery
While Golden has been actively developing antiviral and antiparasitic agents for nearly 20 years, the molecules that are part of this work were not initially intended to target N. fowleri. The Golden Research Group creates new chemistry that builds unique, nature-inspired molecules.
“By designing compounds based on selected motifs found in nature, we are using templates that are already successful in medicine,” she explains. “However, by changing the architecture, we are able to explore different biology.”
“By designing compounds based on selected motifs found in nature, we are using templates that are already successful in medicine.”
—Jennifer Golden
In this case, the chemistry and structural changes resulted in potent inhibitors of N. fowleri.
“Now we are refining the molecules so they possess the right balance of properties likely to make them successful drugs against this infection,” she says.
Those properties include overcoming multiple barriers, such as passing into the brain, where the amoeba causes damage. Fortunately, Golden has extensive experience in this area as the inventor of different small molecules that prevent and treat other rare brain infections, including eastern equine encephalitis (also known as Triple E), a mosquito-borne virus that results in an infection that causes death in more than 50% of cases.
“Unfortunately, the small molecules that treat that viral brain infection do not affect the amoeba,” Golden says. “That’s why this National Institutes of Health funding that supports this amoeba research is critical and timely, as we are seeing the yearly uptick in reported cases of amoeba-related encephalitis. We can’t advance compounds through a pipeline, understand how they work best, and optimize them to serve people unless we have this funding.”
With the new grant, Golden’s team can test the compounds’ efficacy and safety in preclinical models while also understanding important mechanistic details about how to best target the amoeba. If proven effective through those models, their novel compound could be fast-tracked as a potential treatment for patients in dire need.
“We’re still in the early stages,” Golden says. “There are a lot of unanswered questions, but we’re avidly pursuing these promising compounds. It is imperative that we develop effective treatments against this infection and help those affected.”
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