Skip to main content
Drugs.com - Go to homepage
Browse all medications:
  • a
  • b
  • c
  • d
  • e
  • f
  • g
  • h
  • i
  • j
  • k
  • l
  • m
  • n
  • o
  • p
  • q
  • r
  • s
  • t
  • u
  • v
  • w
  • x
  • y
  • z
  • 0-9
Advanced Search
Register Sign In
  • Account
    • Sign in
    • Create an account
  • Drugs A-Z
  • Pill Identifier
  • Drug Interaction Checker
  • Compare Drugs
  • News
  • Pro Edition
  • More Resources
  • Help & Support
  1. Home
  2. News
  3. Clinical Trials
  • All News
  • Consumer
  • Pro
  • New Drugs
  • Pipeline
  • Clinical Trials
  • FDA Alerts

Existing Drug Shows Promise as Treatment for Rare Genetic Disorder

May 30, 2024 -- A drug approved to treat certain autoimmune diseases and cancers successfully alleviated symptoms of a rare genetic syndrome called autoimmune polyendocrine syndrome type 1 (APS-1). Researchers identified the treatment based on their discovery that the syndrome is linked to elevated levels of interferon-gamma (IFN-gamma), a protein involved in immune system responses, providing new insights into the role of IFN-gamma in autoimmunity. The study, led by researchers at the National Institutes of Health’s National Institute of Allergy and Infectious Diseases, was published today in the New England Journal of Medicine.

In a three-stage study, conducted in mice and people, the researchers examined how APS-1 causes autoimmune disease. The syndrome is marked by dysfunction of multiple organs, usually beginning in childhood, and is fatal in more than 30% of cases. This inherited syndrome is caused by a deficiency in a gene that keeps the immune system’s T cells from attacking cells of the body, leading to autoimmunity; chronic yeast infections in the skin, nails, and mucous membranes; and insufficient production of hormones from endocrine organs, such as the adrenal glands. Symptoms include stomach irritation, liver inflammation, lung irritation, hair loss, loss of skin coloring, tissue damage, and organ failure.

In the first stage of this study, researchers led by scientists in NIAID’s Laboratory of Clinical Immunology and Microbiology examined the natural history of APS-1 in 110 adults and children. Blood and tissues were analyzed to compare gene and protein expression in people with and without APS-1. They found elevated IFN-gamma responses in the blood and tissues of people with APS-1, indicating that IFN-gamma may play an important role in the disease and providing a pathway to target for treatment.

In the second stage of the study, the scientists examined mice with the same gene deficiency that causes APS-1 in people, finding that the animals also experienced autoimmune tissue damage and elevated IFN-gamma levels. Mice also deficient in the gene for IFN-gamma did not have autoimmune tissue damage, which showed a direct link between IFN-gamma and APS-1 symptoms. With this understanding, the researchers looked for a drug that could be used to lower IFN-gamma activity in people. They selected ruxolitinib, a Janus kinase inhibitor, because it acts by shutting down the pathway driven by IFN-gamma. When ruxolitinib was administered to the mice with the gene deficiency that causes APS-1, IFN-gamma responses were normalized and T cells were prevented from infiltrating tissues and damaging organs. These results showed that ruxolitinib could alleviate effects of the gene deficiency, suggesting that it could be effective for treatment of APS-1 in people.

Cross-sections of lungs from mice with the gene deficiency that causes APS-1, showing damaged tissue in mice not administered ruxolitinib (left) and healthy tissue in mice administered ruxolitinib (right) Black bars represent 1 mm.
Cross-sections of lungs from mice with the gene deficiency that causes APS-1, showing damaged tissue in mice not administered ruxolitinib (left) and healthy tissue in mice administered ruxolitinib (right) Black bars represent 1 mm. NIAID

The researchers administered ruxolitinib, which was supplied by the NIH Clinical Center, to five people—two adults and three children—with APS-1 in the third stage of the study. The dosing and regimens were tailored to the individuals, and the treatments were continued for over a year. The drug was safe and tolerated well, and improvement in symptoms was seen in all study participants. Blood and tissue analyses revealed decreased production of IFN-gamma from T cells, as well as normalized levels of IFN-gamma in the blood. Many APS-1-related symptoms were reduced, including hair loss, oral yeast infections, stomach and bowel irritation, hives, and thyroid inflammation.

The results revealed that normalizing IFN-gamma levels using ruxolitinib could reduce the damaging effects of APS-1 in people. The scientists note that a study with a larger and more diverse group of patients is needed to determine whether ruxolitinib and similar drugs are suitable treatments for individuals with APS-1. They write that understanding the role of IFN-gamma in autoimmunity may lead to the development of treatments for related diseases. This research highlights the importance of finding the causes of and treatments for rare diseases.

Editorial note: APS-1 is also known as polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) in the literature.

Reference

V Oikonomou et al. The role of interferon-gamma in Autoimmune Polyendocrine Syndrome Type 1. New England Journal of Medicine DOI: 10.1056/NEJMoa2312665 (2024).

Who

Michail S. Lionakis, M.D., Sc.D., chief of NIAID’s Fungal Pathogenesis Section and deputy chief of NIAID’s Laboratory of Clinical Immunology and Microbiology, is available to discuss this research.

NIAID conducts and supports research—at NIH, throughout the United States, and worldwide—to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating 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®

Source: NIH

Posted: May 2024

More news resources

  • FDA Medwatch Drug Alerts
  • Daily MedNews
  • News for Health Professionals
  • New Drug Approvals
  • New Drug Applications
  • Clinical Trial Results
  • Generic Drug Approvals

Subscribe to our newsletter

Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.

Recently Approved
  • mNEXSPIKE

    mNEXSPIKE (COVID-19 Vaccine, mRNA) is a vaccine indicated for active...

  • Tryptyr

    Tryptyr (acoltremon) is a first-in-class TRPM8 thermoreceptor agonist indicated...

  • Khindivi

    Khindivi (hydrocortisone) is an oral solution formulation of the approved...

More drug approvals

Subscribe to our newsletters
Select one or more newsletters to continue.
Stay up-to-date
  • Subscribe to RSS feeds
  • Subscribe to email
Drugs.com Mobile App

Access drug & treatment information, identify pills, check interactions and set up personal medication records.

Download the Medication Guide app on iTunes Download the Medication Guide app on the Google Play store
Drugs.com mobile app
Drugs.com
About
  • About Drugs.com
  • Advertising policy
  • Attribution & citations
Terms & privacy
  • Terms of use
  • Editorial policy
  • Privacy policy
Support
  • Help center
  • Sitemap
  • Contact us
  • Subscribe to Drugs.com newsletters
  • Follow Drugs.com on Facebook
  • Follow Drugs.com on Twitter
  • Follow Drugs.com on Instagram
  • Follow Drugs.com on YouTube
  • Follow Drugs.com on Pinterest

Subscribe to our newsletter for the latest medication news, new drug approvals and FDA alerts.

Drugs.com provides accurate and independent information on more than 24,000 prescription drugs, over-the-counter medicines and natural products. This material is provided for educational purposes only and is not intended for medical advice, diagnosis or treatment. Data sources include Micromedex (updated 2 Jun 2025), Cerner Multum™ (updated 2 Jun 2025), ASHP (updated 11 May 2025) and others.
Certified by TRUSTe Verified by TAG This website is certified by AACI. Click to verify. AdChoices - Ad privacy information
Copyright © 2000-2025 Drugs.com. All rights reserved.