Calcilytics Could be Used to Treat Idiopathic Pulmonary Arterial Hypertension

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A recent study from Japan has shown that dividing cells involved in causing idiopathic pulmonary arterial hypertension (IPAH) may be stopped with a new type of drug called a calcilytic. The research could led to new treatments for IPAH. The study, titled Inhibition of Excessive Cell Proliferation by Calcilytics in Idiopathic Pulmonary Arterial Hypertension appeared September 16, 2015 in the online journal PLoS One.

Pulmonary arterial hypertension is a progressive condition that refers to high blood pressure of the lungs that can ultimately lead to death. The term “idiopathic” means that the cause of the disease in a patient is not known. One of the main problems that occurs in IPAH is that cells lining the blood vessels divide too much and cause the blood vessels to become defective. These cells are known as pulmonary arterial smooth muscle cells (PASMCs).

The researchers, led by Aya Tamamura of the Department of Pharmacy, Kinjo Gakuin University, Nagoya, Japan, wanted to try to stop the dividing cells that lead to the progression of the disease. To do this, they decided to inhibit a critical extracellular Ca2+-sensing receptor (CaSR) using a drug known as a calcilytic. This CaSR  allows the blood vessel muscle cells to divide. In people with IPAH, the CaSR seems to be overactive, possibly contributing to the development of the disease. In previous research studies, researchers noted that genetically knocking out the same receptor caused the PASMCs to stop dividing in an animal model of IPAH.

In this current project, the researchers took cells (the PASMCs) from people with IPAH and from people without IPAH. They found that treating the cells with a calcilytic blocked them from dividing in people who had IPAH, but the drug did not have negative effects on cells taken from people without IPAH. When they applied another drug, (called a calcimimetic) that increases activity on the CaCR, the cell division actually increased not only in cells from people with IPAH but also in cells taken from people who did not have IPAH.

In their research report, the investigators remarked “In this investigation, we have shown that calcilytics (NPS2143 and Calhex 231) inhibit the excessive proliferation of PASMCs from IPAH patients, whereas a calcimimetic (R568) enhances the proliferation of PASMCs from IPAH patients as well as from normal subjects and CTEPH patients.”

A calcilytic or other drugs like it might be used in the future to treat IPAH. The authors note “Taken these findings together, calcilytics are a potential candidate for therapeutic drugs for PAH patients.” This would be a greatly needed new intervention for this difficult to treat and potentially fatal medical condition.