Signaling proteins can unleash the potential of drug-based therapies to treat hyperparathyroidism

Researchers at the Duke-NUS School of Medicine in Singapore have discovered "Sema3d", a signaling protein that appears to protect the parathyroid glands from excessive activity, which could lead to the development of a drug that can treat the disease. hyperparathyroidism, a disease that can currently be treated only by surgery. Information on the study was conducted on May 28, 2019 in Singapore by Assistant Professor Manvendra Singh, Corresponding Author of the Cardiovascular and Metabolic Disorders Program at DukeNUS Medical School.

Parathyroids are four small glands located in the neck, behind the larger thyroid, and are responsible for maintaining a healthy blood calcium level through the secretion of parathyroid hormone (PTH). Primary hyperparathyroidism, a condition in which these glands produce excessive PTH, raises blood calcium levels and causes kidney stones, neuropsychiatric disorders, and bone abnormalities, particularly in older women.

The research team found that semaphorin3d (Sema3d), a signaling protein secreted by parathyroid gland development, helps prevent excessive growth. Sema3d has been shown to reduce signaling in the EGFR / ERBB signaling pathway, which is responsible for the growth of parathyroid cells and also known for its role in cancer growth and survival.

Assistant professor Manvendra Singh said, "Few molecules are known to inhibit the growth of the parathyroid and there is no drug available on the market to treat this disease. Surgery is the most common treatment for hyperparathyroidism. However, reoperative surgery in case of persistent or recurrent hyperparathyroidism remains technically difficult because of fibrous scars and deformed anatomy that make it more difficult to identify abnormal parathyroid glands. Patients also have an increased risk of laryngeal nerve injury, cervical bleeding, and postoperative hypocalcemia. "

In a transgenic model lacking the gene that encodes Sema3d, EGFR signaling was activated, leading to parathyroid cell proliferation and development of primary hyperparathyroidism. Deactivation of EGFR signaling with a known anticancer drug resulted in parathyroid tissue returning to normal. The discovery suggests that Sema3d and drugs that can similarly inhibit EGFR signaling could treat hyperparathyroidism.

The research team further believes that the protective role of Sema3d in limiting parathyroid cell proliferation, by suppressing the EGFR / ERBB signaling pathway, could also be applicable to other types of tumors. Additional research could lead to the development of antitumor treatments using Sema3d or other genetically engineered drugs that target the downstream pathways of the protein, the researchers concluded.