North Texas Dentistry Volume 8 Issue 4 2018 ISSUE 4 DE | Page 5

Understanding
Genetic
Dental Diseases
Dentin disorders of the teeth can have a devastat-
ing effect on a person’s quality of life. What if pre-
venting these conditions was as easy as taking a
drink of water? A new $1.7 million NIH grant
brings Texas A&M College of Dentistry researchers
one step closer to that possibility.
Inherited dental diseases affecting dentin might not happen
often, but they wreak havoc on those who must live with them.
One condition known as dentinogenesis imperfecta — DGI —
hampers tooth formation as a result of gene mutations that
impact the proteins found in dentin. The result: disfigured, dis-
colored teeth that wear easily and often fall out; if left untreated,
both physical and emotional suffering can result.
“The enamel in some DGI teeth is totally gone at a pretty early
age, the dentin underneath is exposed and the teeth look
brown,” explains Dr. Yongbo Lu, associate professor in biomed-
ical sciences. The condition happens to one out of every 6,000
to 8,000 people in the U.S., who find their treatment options
an uphill battle, at best. Type II DGI impacts teeth by obliterat-
ing the dental pulp chamber, and Type III affects teeth through
pulp chamber enlargement and thinner dentin.
“All teeth can be affected, and the treatment presents a big chal-
lenge to dental practitioners,” says Lu, who is the contact prin-
cipal investigator on a five-year, $1.7 million National Institutes
of Health – National Institute of Dental and Craniofacial
Research grant aimed at exploring just what goes wrong at the
molecular level with the gene known as dentin sialophospho-
protein — DSPP — to cause the disease. “Moreover, the treat-
ment is a severe financial burden for the family,” he adds.
Initial steps may include restorative and prosthodontic proce-
dures to prevent severe tooth wear, and dental implants can be
considered later if teeth are lost, but these measures come with
a sizeable price tag — in excess of $20,000 per patient — and
that’s not including subsequent maintenance and retreatment,
Lu says.
To help prevent such an outcome for patients, Lu hopes to
accomplish two goals with the study. First, his team will work
Texas A&M College of Dentistry
by Jennifer Fuentes
to confirm a hypothesis on the precise cause of DGI: that the
mutated DSPP accumulates in the endoplasm reticulum, which
acts as the cell’s manufacturing and packaging system. Second,
Lu and Dr. Chunlin Qin, professor in biomedical sciences and
a principal investigator on the project, will see if small mole-
cules can help clear the mutated protein from the endoplasm
reticulum. Specifically, they will test a small molecule known as
4-phenylbutyrate — 4-PBA — on mouse models that mimic
human DGI tooth defects. This same small molecule has been
found to successfully treat children born with urea cycle disor-
ders, among other conditions. The eventual goal is to allow
patients to take a pill — orally or as an additive to food or drink
— that prevents the onset of DGI.
“We expect that treatment with 4-PBA would be short-term
instead of lifelong,” says Lu.
Timing could be a factor.
“It’s difficult to predict what time would be the optimal point
that the medication should be used, because different teeth have
different developing points,” Qin explains. “It takes a space of
over 10 years for all of the teeth to develop. The first permanent
molar, which is one of the most important for chewing, erupts
around age 6; for it to have normal structure you would have to
apply the medicine, the small molecule, before its eruption.
“Small molecules are one of the hot topics in medical research
and treating diseases: They may serve as agonists or antagonists
in regulating key molecules in the pathways associated with cer-
tain diseases.”
Texas A&M College of Dentistry (formerly Baylor College of Dentistry) in Dal-
las is a part of Texas A&M University and Texas A&M Health Science Center.
Founded in 1905, the College of Dentistry is a nationally recognized center
for oral health sciences education, research, specialized patient care and
continuing dental education. Learn more at dentistryinsider.tamhsc.edu or fol-
low @TAMUdental.
Jennifer Fuentes is a communications coordinator at Texas A&M College of
Dentistry. A 2006 graduate of Texas Christian University, she has worked in
the communications and editorial field for 12 years.
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