A protein found naturally in bullfrogs has become the basis for a bullfrog protein saxitoxin antidote that prevented and reversed lethal shellfish poisoning in mice, according to research published on 16 July in Nature Communications. The study, led by Daniel Minor, PhD, and professor in UCSF‘s Cardiovascular Research Institute, could reshape how clinicians respond to one of the world’s most underreported food poisonings.
Saxitoxin, or STX, is produced by algal blooms and accumulates in shellfish. When people eat contaminated shellfish, it causes paralytic shellfish poisoning (PSP), which disrupts the nerve and muscle cells it attacks. Officially, PSP affects around 2,000 people worldwide each year, though experts say the vast majority of cases go unreported. There is currently no approved antidote: as Science News notes, treatment relies on supportive care such as breathing assistance and oxygen, meaning survival often depends on how quickly a patient reaches emergency services.
That is a serious problem for coastal indigenous communities in the US and Canada, who face the highest exposures to red tide through traditional subsistence harvesting, frequently far from hospital care. It is also a concern for recreational shellfish harvesters worldwide, who may consume contaminated shellfish without any warning.
How the Bullfrog Protein Saxitoxin Antidote Works
The protein at the centre of the research is called saxiphilin. Minor’s team found it acts as a molecular sponge, binding tightly to saxitoxin in the bloodstream before the toxin can reach its cellular targets. Earlier approaches to countering STX focused on disrupting the biological processes the toxin uses to shut down nerve cells, or on triggering immune responses against it. Those attempts were largely unsuccessful.
‘It turns out that one naturally occurring protein is all that’s required to take this toxin out of commission,’ Minor said.
In mouse trials, postdoctoral PhD scholars Samantha Nixon and Sandra Zakrzewska tested saxiphilin against lethal doses of STX. When the protein was given before or alongside the toxin, it prevented poisoning entirely. More encouragingly, saxiphilin also cured nearly all mice that received it after STX exposure, the scenario that best mirrors what happens when a person unknowingly eats contaminated shellfish and seeks treatment only once symptoms begin.
Minor had been uncertain that approach would work. ‘We had this really big protein that needed to catch up with a tiny toxin molecule that has a running start on it,’ he said. ‘We really weren’t sure this was going to work.’ The protein not only improved survival but also reduced the symptoms of severe poisoning, with no harmful side effects observed. Crucially, saxiphilin was found to spread throughout the body, reaching the brain, heart and muscles, allowing it to intercept the toxin wherever it had travelled.
A Broad Target: More Than 50 Toxin Variants
STX is not a single compound but a family of more than 50 closely related variants. In two studies published in 2025 and 2026, Minor showed that saxiphilin can bind a wide range of these variants, which strengthens its case as a genuine antidote candidate rather than one tuned to a single form of the toxin.
The protein occurs naturally in several frog species. According to the NOAA National Centers for Coastal Ocean Science, both the American bullfrog and the High Himalaya frog produce saxiphilins in their blood, suggesting the trait evolved independently across geographically distinct species facing similar environmental pressures.
The current study builds on 2021 research in which Minor and colleagues first demonstrated that saxiphilin binds strongly to saxitoxin and blocks its toxic properties. What remained unknown was whether that binding interaction would be effective inside a living organism. The mouse results confirmed it was.
Minor’s next step is to investigate whether smaller, engineered versions of saxiphilin could offer the same protection across the full range of STX variants. He sees the work as a model for tackling other natural toxins that currently have no antidote. ‘Nature has had to solve this problem multiple times,’ he said. ‘So, there is resilience to toxins all over the biological world.’
The team’s next goal is determining whether those smaller engineered molecules can match or exceed the performance of the full-size protein, a question that will shape whether this moves from mouse studies towards human trials.
