Cortexyme is excited about their possible new treatment, although it has not shown that it 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.
It was believed that AD is caused by the buildup of toxic amyloid plaques in the brain, but numerous therapies blocking amyloid have failed to halt progression of the brain wasting disease in trials, and many now think that this protein may be a side effect of the disease not its root cause.
The company believes this disease may be due to Porphyromonas gingivalis bacteria which is better known for causing gum disease that somehow gets into the brain and sparks inflammation. This microbe and its toxins have been found to be at somewhat higher levels in those with the condition, and it is able to trigger amyloid build up in mice brains.
The company has developed COR388 which is an oral medicine that blocks activity of toxins released by this bacteria. Short safety trials were carried out in 2018 involving healthy volunteers and 9 with mild to moderate Alzheimer’s disease, of which 6 received capsules twice a day and the rest received placebos for 4 weeks.
There were small improvements in 2 dementia severity tests for those who received treatment but they were too small to be classified as statistically significant; but according to the company there were decreases in RANTES found in the blood which is a marker of inflammation, and decreases in ApoE which is damaged by bacterial toxins in the spinal fluid known to play a role in AD.
In those in the treated group there were also improvements in some aspects of computer testing to assess speech, in 3 out of 35 measures the gains were significant which best predict cognitive decline.
Improvements in biomarkers doesn’t mean they will translate into reduced symptoms, as there have been many false hopes in former trials and other approaches. “We definitely need some more data before we can understand the consequences of having this bacteria in the brain,” says Routledge.
Cortexyme has now started a larger study involving 570 Alzheimer’s patients that will be a year long with results due in 2 years; and a different company is developing a vaccine against this bacteria.
