Could Targeting Gum Disease Bacteria Slow Alzheimer’s?
Intriguing lines of evidence have implicated gingivitis bacteria as a potential contributor to Alzheimer’s. Now Lighthouse Pharma is testing if a drug that stops it could treat the disease.
The drug company Lighthouse Pharma suspects that Porphymonas gingivalis, a bacteria that causes gum disease, might trigger Alzheimer’s. They’ve begun recruiting participants for its Phase 2 trial of a drug called LHP588 that could stop the bacteria from thriving in the brain.
The idea builds on longstanding evidence linking gum disease to higher Alzheimer’s risk. Since the hallmark proteins of Alzheimer’s, beta-amyloid and tau, have antimicrobial properties, scientists speculate that when P. gingivalis reaches the brain, it spurs their buildup and other disease processes. P. gingivalis releases gingipains, enzymes called proteases that degrade the body’s defenses, drive inflammation, and help the bacteria thrive.
Lighthouse Pharma has secured a $49.2 million grant from the National Institute of Aging in August 2025 to fund this trial.
Gum health and Alzheimer’s risk
Many Alzheimer’s drug trials arise out of observational research. In this case, across many electronic health records studies, poor gum health is linked to a higher risk of Alzheimer’s — especially in the more advanced stages.
“Of course the more someone is impacted by dementia, the more they struggle with their own self care,” Dr. Glen Finney, director of the Geisinger Memory and Cognition Program and a fellow of the American Academy of Neurology told Being Patient. “Are they having worse Alzheimer’s because of their gingivitis, or are they having more gingivitis because of Alzheimer’s?”
Does P. gingivalis reach the brain?
Lighthouse Pharma’s approach assumes that P. gingivalis and its gingipains could get into the brain. In animal models of Alzheimer’s, the bacterium can reach the brain but in humans, the evidence is more limited.
Some studies have found evidence of both the bacteria and gingipains in the brains of people with Alzheimer’s. Another failed to find evidence of gingipains in autopsied Alzheimer’s brains, but found that 40% had another protein secreted by P. gingivalis. A third found no evidence of P. gingivalis in the blood or cerebrospinal fluid. The discrepancies might be attributed to different methods and techniques and small sample sizes between 10 to 20 participants.
Sim Singrhao, a visiting fellow at the University of Lancashire, told Being Patient that it isn’t clear yet whether the entire bacteria gets into the brain. “So far, no researcher has captured an image proving that whole P. gingivalis cells are present inside brain tissue, even though its DNA has been detected there,” Singhrao said.
She believes it’s more likely that the bacteria sends gingipains and other components packaged inside of fatty globules called outer-membrane vesicles. While the idea that gingipains might be contributing to Alzheimer’s is intriguing, Rao cautioned that “targeting gingipains alone may not be sufficient” for treatment.
Testing gingipain inhibitors in Alzheimer’s
This approach might feel like deja vu. The drug company Cortexyme (now Quince Therapeutics) tested the experimental gingipain inhibitor atuzaginstat in a Phase 2/3 trial years ago. Many participants who received high doses developed liver problems. .
When the data was reported in 2021, the drug failed to meet both of its main outcome measures. The participants receiving the highest dose of the medication declined only 1.9 points (on a 70 point scale of cognitive function) after 48 weeks of treatment, compared to placebo — a change considered too small to be noticeable by patients and caregivers. There was no improvement on a scale of daily living activities.
“One negative trial may be premature to give up on a treatment,” Finney said. “You need to learn from those negative trials.”
Despite the negative data, the drug company found that a subgroup of participants who had tested positive for P. gingivalis showed more improvement. But Cortexyme discontinued the development program and sold off its portfolio to Lighthouse Pharma, a new company founded by Cortexyme’s former CEO.
Lighthouse Pharma has now started recruitment for a Phase 2 trial of a newer gingipain inhibitor called LHP588, which doesn’t seem to show the same side effects on the liver. The company aims to recruit 300 participants with mild to moderate Alzheimer’s that test positive for P. gingivalis on a saliva test. The trial is expected to finish in 2030.
Whether or not the trial succeeds, Finney noted that there are many important health benefits to taking care of your gums. “You don’t need to wait for clinical trials,” he said.
