Alzheimer’s disease is a global public health threat, affecting more than 30 million people worldwide and 5.7 million in the United States. While the number of people with the disease continues to climb, the few medications that are currently available only provide temporary symptom relief without slowing progression of the disease. To date, potential new treatments have not been effective in clinical trials.
Recent scientific discoveries, described below, have led to a new understanding of the cause of Alzheimer’s disease that could revolutionize the way that it is treated.
Scientific experts have discovered that a bacteria called P. gingivalis, most commonly associated with degenerative gum disease, can infect the brain in older people who are more susceptible to infection. Once in the brain the bacteria releases toxic proteins, called gingipains, that have been shown to destroy neurons and cause other signature signs of Alzheimer’s disease in the brain in animal studies. Once the brain is infected, the brain’s natural defenses gather around the infected cells causing the inflammation and buildup of plaques associated with Alzheimer’s disease.
A recent study found that more than 90 percent of patients with Alzheimer’s disease had evidence of P. gingivalisbacteria and its toxins in their central nervous system. Tests in mice demonstrated that the bacteria could travel from the mouth to the brain and increase production of brain plaques, inflammation and damage to neurons associated with Alzheimer’s disease.
At Cortexyme, we are developing therapies based on this new understanding of P. gingivalis infection as a potential cause of Alzheimer’s disease. We have designed COR388 to block toxic proteins, called gingipains, created by the bacteria and to stop or slow further damage to healthy brain cells.
In a study of mice infected with the P. gingivalis bacteria, COR388 reduced the infection, blocked the production of toxic proteins in the brain, reduced amyloid beta levels, which result in plaque, reduced markers of inflammation and halted progression of neuronal degeneration.
At Cortexyme, we previously conducted a clinical study administering COR388 or placebo for 10 days to 24 healthy older volunteers, and for 28 days to nine subjects with Alzheimer’s disease. COR388 was well-tolerated with no clinically significant trends in adverse events or concerning safety signals. DNA of the P. gingivalis bacteria was found in the cerebrospinal fluid in all subjects with Alzheimer’s disease analyzed in the study. In addition, there was a promising trend of average improvement in the memory test performance for the Alzheimer’s patients in the study who were administered COR388 compared to placebo.