Promising Results: NIH-Supported Clinical Trial Offers Hope for Effective Treatment of Rare Genetic Disease

Drug Shows Promise in Slowing Progression of Rare Genetic Disease

Wednesday, April 3, 2024

A drug previously used in the treatment of certain bone diseases has shown promise in slowing the progression of a rare, painful genetic condition that causes excessive calcium buildup in the arteries. This breakthrough could potentially lead to the development of the first effective treatment for the disease.

What is ACDC disease?

Arterial calcification due to deficiency of CD73 (ACDC) is a rare condition characterized by the abnormal accumulation of calcium in the arteries, mainly targeting the legs. This abnormal buildup can cause severe pain, difficulty in walking, and potential limb loss. ACDC disease also affects the joints of the hands, leading to pain and deformities. It is an extremely rare disease, with an estimated prevalence of less than 1 in 1 million, and is believed to affect only around 20 people worldwide.

Despite ongoing research, ACDC disease currently has no known cure. However, recent studies by the National Heart, Lung, and Blood Institute (NHLBI) have identified a potential treatment option. Researchers have found that an existing drug called etidronate, typically used for other bone conditions, may have therapeutic effects for ACDC based on animal and human cell models.

Progress in the Clinical Trial

In a first-in-human clinical trial supported by the NHLBI, researchers investigated the safety and effectiveness of etidronate in treating calcification of the arteries and impaired blood flow in the legs of seven ACDC patients. This patient sample represents about one-third of all known ACDC cases worldwide. The treatment involved a daily oral intake of etidronate for 14 days every three months over a three-year period.

The results of the trial demonstrated that etidronate is safe for ACDC patients, with no reported adverse side effects. While the drug appeared to slow the progression of new calcium deposits in the blood vessels of the legs and inhibit the progression of blood flow impairment, it did not alleviate existing calcium deposits or significantly improve blood flow. Patient reports did suggest a moderate improvement in symptoms, such as pain and motion impairment.

Potential Implications of the Study

The insights gained from this study have significant implications for the future development of novel therapies and larger clinical trials for ACDC disease. Moreover, the study findings could shed light on other diseases that involve the excessive buildup of calcium in the arteries, such as peripheral artery disease and atherosclerosis.

References

Ferrante EA, Cudrici CD, Rashidi M, et al. Pilot study to evaluate the safety and effectiveness of etidronate treatment for arterial calcification due to deficiency of CD73 (ACDC). Vascular Medicine. 2024. doi: 10.1177/1358863X241235669

Contributors

This study was led by Elisa Ferrante, Ph.D., clinical program manager and staff scientist in the Translational Vascular Medicine Branch at the NHLBI, and Alessandra Brofferio, M.D., clinical cardiologist with the Laboratory of Cardiovascular Regenerative Medicine at the NHLBI.

About the National Heart, Lung, and Blood Institute (NHLBI)

The National Heart, Lung, and Blood Institute (NHLBI) is a global leader in conducting and supporting research on heart, lung, and blood diseases, as well as sleep disorders. Their mission is to advance scientific knowledge, improve public health, and ultimately save lives. For more information, visit www.nhlbi.nih.gov.

About the National Institutes of Health (NIH)

The National Institutes of Health (NIH) is the primary federal agency for medical research, consisting of 27 Institutes and Centers. Under the U.S. Department of Health and Human Services, the NIH conducts and supports fundamental, clinical, and translational medical research to investigate the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

NIH… Turning Discovery Into Health^®