Focus on dental research: Let knowledge conquer disease

The English translation of the Latin motto Vincat Scientia Morbos, “Let knowledge conquer disease,” is frequently used in medical and dental science education to highlight the power of research, learning and evidence-based practice.

Unfortunately, in comparison to the general field of medicine, dentistry receives a comparatively small amount of overall research funding, with research from 2022 showing that National Health and Medical Research Council (NHMRC) funding for dental disorders between 2017 to 2021 was $15 million, which equated to only 0.23 per cent of NHMRC funding for the top 75 diseases with the highest disease burden. (1)

Heart disease, diabetes and dementia tend to dominate this space, both in headlines and in grant dollars. However, the burden of untreated oral disease on individuals, the health system and the economy is significant.

The Australian Dental Research Foundation has spent over five decades working against that imbalance, and research from Associate Professor Munira Xaymardan (pictured lower right, above, with her team) is a clear example of what a modest grant, placed early, can grow into.

A groundbreaking discovery

Dr Xaymardan spent eight years in full-time dental practice before moving into academia. Her recent research began with a question about congenital syndromes.

Down syndrome, DiGeorge syndrome and Pierre Robin syndrome all link facial and cardiac abnormalities, and while the genetic basis for some is well understood, the underlying biological connection was not.

“I wanted to look at this correlation,” says Dr Xaymardan, who made a profound discovery: Cells from the heart field migrate to the orofacial area during embryonic development via structures called pharyngeal arches, carrying distinct gene markers of cell population that bear heart muscle stem cells.

Unlike the heart itself, which has no capacity to regenerate after a heart attack and instead repairs by scarring, these migrated cells remain in the orofacial muscle, where they can be isolated and coaxed into becoming cardiomyocytes, the cells that make up heart muscle.

“The heart doesn’t have stem cells,” Dr Xaymardan explains. “But the orofacial tissues have this stem cell migrated in embryos, still existing in the adult facial muscle, that we can be isolated and differentiated into cardiomyocytes.”

This research began with an $8,000 grant from the Australian Dental Research Foundation, when Dr Xaymardan moved her research program from the Victor Chang Cardiac Research Institute to the University of Sydney’s dental school. The funding was enough to seed fund two PhD students’ laboratory consumables and start testing the theory.

Since then, the project has been validated in vitro and in small animal models in collaboration with the Victor Chang Cardiac Research Institute, with a provisional patent now in place. The next stage, moving toward preclinical trials, will need substantially more funding. But it would not exist at all without that initial ADRF support.

“For a proof of concept, a small amount can make a big difference,” Dr Xaymardan says. “ADRF grants have sustained the Australian dental school research laboratories and graduated so many PhD students that become core academic workforce of dental research and education in Australia, and this has been the only stable source for dental research in Australian universities.”

A hidden clue to infant health

A second, linked but separate line of Dr Xaymardan’s research, also supported with the help of ADRF funding, is investigating what happens when a pregnant woman has untreated periodontitis.

Using an animal model that closely replicates human periodontal disease, Dr Xaymardan’s team found mice with periodontitis had lower birth weight, lower placental and embryonic weight in mid-gestation and higher rates of neonatal mortality. When researching why, they found periodontitis-associated bacteria travel to the placenta and alter its blood vessels, a plausible mechanism for the foetal harm observed.

“A gum infection in a pregnant woman can affect an unborn child,” Dr Xaymardan explains. It’s a finding with precedent elsewhere in maternal health, as children born to mothers with diabetes or autoimmune disease face higher risks of low birth weight, premature birth and later health problems. Dr Xaymardan’s work suggests periodontal disease as a systemic chronic inflammatory disease is being overlooked as part of that same conversation.

The discovery is being tested further. Dr Xaymardan’s lab, based at Westmead Hospital, is now collaborating with maternal and foetal medicine specialists on a clinical study tracking early pregnancy patients for links between periodontitis and complications including gestational diabetes and preeclampsia. Of the roughly 80 women seen so far, only 21 percent had healthy gums, 38 percent had gingivitis, and around 41 percent, women mostly in their twenties and thirties, had periodontitis.

“You have your blood pressure checks when you’re pregnant, you have your diabetes [screening],” Dr Xaymardan says. “But nobody says you need a dental appointment at any stage.” Two of the women included the study who had already had a miscarriage unknowingly had serious gum disease. Because doctors aren’t required to refer pregnant patients for dental checks, women with periodontitis often go overlooked until well into pregnancy, when intervention can be harder.

“We need to look after the woman, even pre-pregnancy,” Dr Xaymardan says. “It’s much less cost than looking after an unhealthy-born baby for life.”

Research is ongoing, with the anticipation that being able to demonstrate a larger scale of data will lead to more government and industrial funds to expand the impact of the studies.

From small grants to big outcomes

Dr Xaymardan sits on the ADRF’s Board of Directors and chairs its Research Advisory Committee, giving her a rare vantage point on both sides of the process: as a researcher who built research projects on ADRF seed funding, and as someone who now coordinates assessment of the research applications.

As she explains, dental and oral health research competes for attention against conditions with obvious immediate mortality data, such as heart disease, diabetes and dementia. Oral disease rarely kills directly, so it struggles to attract the same funding priority, even though the downstream health and economic burden is significant.

“Oral concerns are not dementia, not heart disease, not diabetes,” Dr Xaymardan says. “You can’t show direct mortality or morbidity; you don’t get the same level of priority. But indirectly, it does have huge impact on the community by aiding the progression of the disease with high mortality and morbidity.”

As she explains, major organisations such as the NHMRC and Australian Research Council won’t back a project that lacks preliminary data. The ADRF’s small grants help to generate exactly that evidence, giving researchers a foothold to pursue larger funding elsewhere.

“The smallest amount of research can literally change lives, potentially for hundreds of thousands of people,’ says Dr Xaymardan, “and help open the door to the knowledge that conquers disease.”