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NIH Record - National Institutes of Health

Investigational Drug Restores Parathyroid Function in Rare Disease

A doctor in a surgical mask conducts an exam on a patient in a surgical mask

NIDCR’s Dr. Rachel Gafni examines a clinical trial participant with ADH1, a rare genetic disorder marked by abnormally low levels of calcium in the blood.

Photo: NIDCR

An investigational drug, encaleret, restored calcium levels in people with autosomal dominant hypocalcemia type 1 (ADH1), a rare genetic disorder marked by an imbalance of calcium in the blood and urine. People with ADH1 have abnormally low levels of parathyroid hormone, which regulates blood calcium levels. 

Results from this clinical trial, led by clinician-scientists from NIDCR at the Clinical Center, are published in the New England Journal of Medicine.

In the mid-phase clinical trial, 13 participants with ADH1 received oral doses of the investigational drug for about 24 weeks. By the end of the trial, the treatment restored every participant’s blood calcium level to normal, and urine calcium approached normal levels. Parathyroid hormone levels also normalized.

“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 Dr. Michael Collins, an NIDCR endocrinologist.

People with ADH1 have unusually low calcium levels in the blood, leading to symptoms that can range from tingling limbs, muscle cramps and brain fog to life-threatening seizures. Currently, no approved treatments address the root cause of the condition.

“Conventional therapy is to raise the blood calcium level with calcium supplements and activated vitamin D,” said principal investigator and NIDCR pediatric endocrinologist Dr. Rachel Gafni. “However, too much of an increase could cause kidney damage…The patients need better treatments.”

Encaleret is thought to exert its effects by acting on faulty calcium-sensing receptors that are peppered throughout the kidneys and pea-sized organs in the neck called parathyroid glands. In healthy people, these receptors monitor and control calcium levels. However, in patients with ADH1, the parathyroid glands do not make enough parathyroid hormone and the kidneys flush too much calcium out of the body, leading to low calcium levels in the blood and high levels in the urine.

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