Gum disease bug and the development of Alzheimer’s
Scientists researching Alzheimer’s disease say they believe bacteria which cause gum disease may be linked to the condition – and that they may have found a treatment.
The team of researchers from the US, Australia, New Zealand, Poland and Norway say their evidence suggests a link between porphyromonas gingivalis – the most common cause of chronic periodontitis, which can lead to tooth loss, in humans – and the degenerative brain condition. And when they tested a new drug that blocks toxic enzymes produced by the bacteria, called gingipains, on mice, they were able to halt the damage.
Dr Stephen Dominy, one of the study authors and co-founder of the US company Cortexyme, which developed the drug, called COR388, described the evidence as “solid” – despite the often very small sample sizes involved in the study and the fact that clinical trials on humans have not been completed.
Writing in the journal Science Advances, where they published their findings, the scientists said:
“The findings of this study offer evidence that porphyromonas gingivalis and gingipains in the brain play a central role in the pathogenesis of Alzheimer’s disease.”
Analysis and experimentation
The scientists analysed brain tissue, spinal fluid and saliva from dead and living patients with diagnosed and suspected Alzheimer’s, and found evidence of both gingipains and porphyromonas gingivalis DNA.
In experiments on mice, they found that gingipains damaged tau – a protein needed for normal neuronal function. Cells infected with porphyromonas gingivalis showed a loss of tau within one hour.
By targeting gingipains, the new drug both reduced the amount of bacteria in the brain, and stopped the degeneration of neurons in the hippocampus – a part of the brain associated with long term memory, and one of the first areas to be damaged by Alzheimer’s. It also reduced brain inflammation, which is found in Alzheimer’s patients.
The suggestion that porphyromonas gingivalis may play a role in Alzheimer’s is not new. A previous observational study of Alzheimer’s patients found that the cognitive function of those with chronic periodontitis declined significantly more over a six-month period compared to those not suffering from it.
The bacteria can occur at low levels in one in four healthy people with no oral disease, and can be found elsewhere in the body. In the mice tests, the bacteria made it into the brain despite the mice having been orally infected.
Antibiotics rarely eradicate it – in the mice tests, the antibiotics moxifloxacin and doxycycline did not stop the bacteria from damaging brain cells, and the bacteria became resistant to the moxifloxacin. The scientist suggest that porphyromonas gingivalis spreads via several pathways to the brain and then from neuron to neuron over a period of many years.
Experts advise caution
Despite the apparent good news, Alzheimer’s experts urged caution. Dr David Reynolds, chief scientific officer at Alzheimer’s Research UK, said: “The presence of a single type of bacteria is extremely unlikely to be the only cause of the condition.”
Dr James Pickett, head of research at the Alzheimer’s Society, added: “The laboratory work does suggest that this infection could cause damage to cells of the brain but there isn’t yet clear evidence that it can cause this damage in people or result in Alzheimer’s.
“Success of this new drug depends on whether the infection really does play an important role in Alzheimer’s disease. It’s important to pursue that as there hasn’t been a new drug for dementia in 15 years.”
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