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People with ADH1 have unusually low blood calcium, leading to symptoms like tingling limbs, muscle cramps, brain fog, and even fatal seizures.
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Encaleret Restores Parathyroid Function in ADH1 Trial

Some 3.9 in 100,000 people in the US are affected by ADH1, a major cause of nonsurgical hypoparathyroidism

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Swathi Kodaikal, MSc

Swathi Kodaikal, MSc, holds a master’s degree in biotechnology and has worked in places where actual science and research happen. Blending her love for writing with science, Swathi enjoys demystifying complex research findings for readers from all walks of life. On the days she doesn’t write, she learns and performs Kathak, sings, makes plans to travel, and obsesses over cleanliness.

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Published:Oct 26, 2023
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“It was amazing to see that every participant responded to the treatment. In literally minutes after taking the medication orally, the levels of parathyroid hormone increased dramatically,” said senior author and National Institute of Dental and Craniofacial Research (NIDCR) endocrinologist Michael Collins, MD, in a recent press release about the efficacy of an investigational drug to treat autosomal dominant hypocalcemia type 1 (ADH1), a rare genetic disorder.

What happens in the rare disease ADH1?

People with ADH1—a rare form of hypoparathyroidism—have unusually low blood calcium, leading to symptoms like tingling limbs, muscle cramps, brain fog, and even fatal seizures. Inherited or de novo activation of the calcium-sensing receptor (CASR) gene variants alters “the set point for extracellular calcium, resulting in inadequate parathyroid hormone secretion.” This triggers the kidneys to excessively flush off calcium in the urine leading to hypercalciuria.

“Conventional therapy is to raise the blood calcium level with calcium supplements and activated vitamin D,” said principal investigator and NIDCR pediatric endocrinologist Rachel Gafni, MD. “However, too much of an increase could cause kidney stones or damage kidney tissues, leading to kidney failure in worst-case scenarios. The patients need better treatments, so we’re not constantly walking on a tightrope.”

Encaleret: A ray of hope

When administered orally for 24 weeks to 13 participants with ADH1, the investigational drug encaleret restored blood and urine calcium levels to normal in all participants and normalized the parathyroid hormone levels. The drug is thought to act on faulty calcium-sensing receptors that line the kidneys and the parathyroid glands.

Encaleret appeared to be safe and caused no serious side effects in the trial participants. However, since the parathyroid hormone maintains blood calcium levels alternatively by drawing calcium from the bone reserves, the researchers suggest encaleret may affect the skeletal system.

An ongoing clinical trial led by Collins and NIDCR staff clinician Iris Hartley, MD, is investigating whether the treatment can help correct calcium levels in people whose parathyroid glands have been damaged by surgery. “Because ADH1 can be passed on to offspring, the participants are not just doing this for themselves; it’s for their children, grandchildren, and great-grandchildren,” said Gafni. “One day, hopefully, we’ll be writing prescriptions for an effective treatment thanks to them.”