Suppressing Parathyroid Gland Overactivity

A protein known as semaphorin3d was found to inhibit a signaling pathway that promotes parathyroid growth.

AsianScientist (Jun. 13, 2019) – Scientists in Singapore have discovered a signaling protein that may lead to treatments for hyperparathyroidism. Their findings are published in the Journal of Biological Chemistry.

Parathyroid glands control the body’s blood calcium levels, and their overactivity can lead to kidney stones, neuropsychiatric disorders and bone abnormalities, particularly among elderly women. The condition is currently treatable mainly through surgery.

In the present study, a team of scientists at Duke-National University of Singapore Medical School (Duke-NUS) have identified semaphorin3d (Sema3d), a protein secreted by developing parathyroid glands, that could potentially be used to inhibit hyperparathyroidism.

“Not many molecules are known to inhibit parathyroid growth and there are no drugs available in the market to treat the condition,” said Assistant Professor Manvendra Singh at Duke-NUS, a co-author on the study.

“Surgery is the most common treatment for hyperparathyroidism. However, reoperative surgery for persistent or recurrent hyperparathyroidism remains technically challenging due to fibrotic scarring and distorted anatomy that make it more difficult to identify abnormal parathyroid glands. Patients are also at increased risk for laryngeal nerve injury, cervical bleeding and postoperative hypocalcemia,” he added.

In a transgenic mouse model lacking the gene that codes for Sema3d, a cellular switch known as the EGFR signaling pathway was activated, leading to parathyroid cell proliferation and the development of primary hyperparathyroidism. Turning off EGFR signaling with a known anticancer drug caused some of the parathyroid tissue to return to normal. The finding suggests Sema3d and drugs that similarly inhibit EGFR signaling could treat hyperparathyroidism.

“This discovery is a potential game-changer in the treatment of hyperparathyroidism,” said Professor Patrick Casey, senior vice dean for research at Duke-NUS. “Considering the condition is common in the elderly, possible drug-based therapeutic options in the future would reduce the burden of surgery and associated risks in these elderly patients.”

The research team has plans to further examine Sema3d’s protective role in cancer as well. Further investigations could lead to the development of anticancer treatments employing genetically engineered Sema3d or other drugs that target the protein’s downstream pathways.

The article can be found at: Singh et al. (2019) Deficiency in the Secreted Protein Semaphorin3d Causes Abnormal Parathyroid Development in Mice.


Source: Duke-NUS Medical School. Photo: Duke-NUS Medical School.
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