Experimental Alzheimer’s drug targets gum disease bacteria

Encouraging results have been announced from a small trial of a new kind of treatment for Alzheimer’s disease, which targets gum disease bacteria. Trial participants showed improvements in certain molecules in their blood and spinal fluid, says Cortexyme, the US firm developing the therapy.

However, the company has not shown yet that the treatment can reduce the severity of dementia. “It isn’t enough to get excited about, but it’s enough to say this hypothesis is interesting,” says Carol Routledge of the charity Alzheimer’s Research UK.

The new approach is at odds with decades of thinking about Alzheimer’s. It was believed that the condition is caused by a build-up of toxic plaques in the brain made of a protein called amyloid. But numerous therapies that blocked amyloid failed to halt progression of the disease in trials, and many researchers now think the protein may be a side effect of Alzheimer’s, not the root cause.

Cortexyme thinks that Alzheimer’s may be due to bacteria called Porphyromonas gingivalis – better known for causing gum disease – somehow getting into the brain and sparking inflammation. The microbe and its toxins have been found at somewhat higher levels in the brains of people with Alzheimer’s, and can trigger amyloid build-up if put into the brains of mice.

Reduced inflammation

Cortexyme has developed an oral medicine called COR388 that can block the activity of toxins released by the bacteria. Last year, the firm carried out short trials in healthy volunteers and nine people with mild to moderate Alzheimer’s disease, six of whom got twice-daily capsules, while the rest got a placebo version.

After four weeks, there were small improvements in two kinds of tests for dementia severity for those who got the medicine, but these were too small to be classed as statistically significant. Cortexyme says that is because the trial was designed as a safety test and was too small to show efficacy.

However, there were falls in a marker of inflammation called RANTES found in the blood, the firm told the Alzheimer’s Association International Conference in Los Angeles today. Inflammation is known to be linked to Alzheimer’s.

The firm also saw a drop in fragments of a protein called ApoE, which is damaged by the bacterial toxin, in people’s spinal fluid. ApoE is known to play a role in Alzheimer’s: people who make a particular genetic variant of the protein are more likely to develop the condition.

The drop in RANTES and ApoE fragments would suggest the medicine is working as intended, Mike Detke, Cortexyme’s chief medical officer, told New Scientist. “It’s very promising.”

Larger trial

The treated group also showed improvements in some aspects of a test that uses a computer to assess speech. In three out of 35 measures, the gains were significant. “The three that showed effects were ones which have been best predictive of cognitive decline,” says Detke.

Routledge says we shouldn’t assume improvements in substances in blood or spinal fluid – sometimes called “biomarkers” – will translate into reduced dementia symptoms, as similar ones have given false hope in past trials of other approaches. “We definitely need some more data before we can understand the consequences of having this bacteria in the brain,” she says.

The firm has now begun a year-long trial in 570 people with Alzheimer’s disease, which is due to give results in two years. A different firm is developing a vaccine against the bacteria.