Around 4.9 million children around the world are born with birth defects each year.
Professor Sally Dunwoodie is hoping to curb this statistic by determining the extent to which the vital molecule Nicotinamide Adenine Dinucleotide (NAD) deficiency is the cause of miscarriage and congential malformation. Prof Dunwoodie established and leads the largest Australian genome sequencing initiative in congenital heart disease, the Chain Reaction Program in Congenital Heart Disease at the Victor Chang Cardiac Research Institute, and is the recipient of St Vincent’s Clinic Foundation’s 25 Year Anniversary Grant.
Prof Dunwoodie made global news last year when 12 years of research resulted in the world first discovery that two particular genes, named HAAO and KYNU, both of which are found in humans and mice, worked together in the same pathway to create NAD. The lengthy research focussed on four unrelated families with four babies, all born with serious heart, vertebral and kidney defects. After sequencing the genes of those babies, their unaffected parents and siblings - which revealed that two of these babies had a mutation in the HAAO gene and two in KYNU - Professor Dunwoodie then set to work in the laboratory with mutations of these genes in mice.
“We realised 'we are on to something really special here’,” she recalls. “What we then did was make mice that had a mutation in the HAAO gene and other mice that had mutation in the KYNU gene and these mice ended up with the same birth defects as humans. So, there was proof we were on to the right thing. We then showed that both the humans and mice were deficient in NAD.”
Combining this with the knowledge that the human body can make enough NAD if it is given additional vitamin B3, she then gave the mice with these mutated genes vitamin B3 to see the effects.
The St Vincent’s Clinic Foundation grant provided crucial funding for some of the important, ongoing research that has Professor Dunwoodie now looking at 95 other genes that may play a role in making NAD. Despite their genetic mutation, the mice developed completely normal embryos. “It is very rare to find new causes of birth defects, in terms of new gene mutations, and at the same time, work out the mechanism as to why there are birth defects: because there was a deficiency in NAD. “And it is extremely rare to come up with a preventative, which is vitamin B3”.