Could pills control a genetic ailment that disfigures and discolors teeth?

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A federally funded study may allow biomedical scientists at Texas A&M University’s College of Dentistry to identify exactly what triggers an inherited condition known as dentinogenesis imperfecta, or DGI. Their long-term goal is to create an oral treatment that prevents the onset of DGI.

DGI hampers tooth formation as a result of gene mutations that impact the proteins found in dentin. The result: disfigured, discolored 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,” says Yongbo Lu, associate professor in biomedical sciences. The condition happens to one out of every 6,000 to 8,000 people in the United States, who find their treatment options an uphill battle, at best. Type II DGI harms teeth by obliterating 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 challenge to dental practitioners,” says Lu, who is the contact principal investigator on a five-year, $1.7 million National Institutes of Health – National Institute of Dental and Craniofacial Research grant aimed at discovering just what goes wrong with the gene known as dentin sialophosphoprotein — DSPP — to cause the disease.

Lu hopes to accomplish two goals with the study.

First, his team will work 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 Chunlin Qin, professor in biomedical sciences and a principal investigator on the project, will see if small molecules 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 disorders, among other conditions.

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