A new study by researchers at the University of Maryland School of Medicine (UM SOM) has found a link between some neurodegenerative diseases and a birth defect that occurs commonly in infants of women with diabetes. This is the first time this link has been identified; it may indicate a new way to understand, and perhaps treat, both the birth defects and the neurodegenerative diseases.

The findings were published recently in the Proceedings of the National Academy of Sciences journal.

“These results were really surprising,” said the study’s lead author, Zhiyong Zhao, PhD, an Associate Professor of the Department of Obstetrics, Gynecology and Reproductive Sciences at UM SOM. “The association suggests that these disparate diseases may have more in common than we previously realized.” The researchers on the article also include UM SOM Dean E. Albert Reece, MD, PhD, MBA, and Lixue Cao, PhD, a Postdoctoral Fellow in the Department of Obstetrics, Gynecology and Reproductive Sciences at UM SOM.

Neural tube defects occur when misfolded proteins accumulate in the cells of the developing nervous system. The misfolded proteins form insoluble clumps, known as aggregates, which cause widespread cell death, eventually leading to birth defects. Protein aggregates also play a major role in Alzheimer’s, Parkinson’s and Huntington’s disease. In Alzheimer’s, for instance, this leads to the accumulation of plaques in the brain, reducing the ability of that organ to function.

The researchers studied pregnant mice with diabetes, and found that their embryos contained aggregates of at least three misfolded proteins that are also associated with the three neurodegenerative diseases: alpha–Synuclein, Parkin, and Huntingtin. It is not clear exactly how these protein aggregates contribute to those diseases, but the link is well established.

This latest research also underscores the links between diabetes and some neurodegenerative diseases. People with diabetes have a higher risk of Alzheimer’s and Parkinson’s disease, and some research suggests that there are molecular links between Huntington’s and diabetes as well.

The scientists also examined whether it is possible to reduce levels of the misfolded proteins, and in so doing reduce neural tube defects. They gave diabetic pregnant animals sodium 4–phenylbutyrate (PBA), a compound that can reduce mistakes in molecular structure by aiding the molecules that ensure proper protein folding. In the animals that received PBA, there was significantly less protein misfolding, and fewer neural tube defects in the embryos. PBA has already been approved by the US Food and Drug Administration for other uses, and if it proves safe and effective in humans for this purpose, it could potentially reach patients much more quickly than an entirely new drug.