# PHOX2B Congenital Central Hypoventilation Syndrome (CCHS) Physiologic Signatures in Readiness for Future Clinical Trials

> **NIH NIH R03** · LURIE CHILDREN'S HOSPITAL OF CHICAGO · 2022 · $77,500

## Abstract

Project Abstract
Congenital central hypoventilation syndrome (CCHS)(OMIM #209880), a rare and severe neurocristopathy
typically presenting in the newborn period and characterized by profound hypoventilation and impaired automatic
control of breathing, necessitates life-long artificial ventilation. Neurocognitive outcome is often compromised
due at least in part to the impact of repetitive hypoxic and hypercarbic exposure. Patients suffer from a spectrum
of severe symptoms compatible with autonomic dysregulation. Currently, no pharmacologic interventions have
been demonstrated to decrease disease burden in CCHS, and the limited treatment options available are highly
invasive, burdensome and offer only palliative support. Long considered a congenital disease with little hope for
long-term improvement, mounting evidence suggests that many aspects of the CCHS phenotype are part of
ongoing disease processes that develop over time and are sensitive to intervention. Recent CCHS cases have
been reported who appeared normal until a precipitation factor, such as respiratory infection or anesthetic
exposure. These cases indicate that at least some CCHS patients maintain the physiologic potential to function
without artificial ventilation and offer hope that some severe aspects of CCHS could be reversed. Potential for
therapeutic intervention has been highlighted by reports of successful off-label drug use in CCHS case reports,
cellular models indicating potential for reversing CCHS-related pathogenic processes, and development and
approval of devices in other disease populations that have game-changing potential in CCHS. Currently, gold-
standard assessment of disease stability and progression requires inpatient admission and specialized testing
at one of only a handful of referral centers with CCHS expertise. Given the rarity and geographic dispersion of
CCHS patients, this limits potential for clinical trials to assess potential therapeutics. Over several decades of
providing care to CCHS patients, we have developed a data set that includes detailed medical records, annual
testing including labwork, 72-hour Holter recordings, comprehensive physiologic in-laboratory 4-day and 4-night
recordings, and neurocognitive testing for a cohort of >85 patients and >350 admissions, representing the world’s
largest CCHS cohort with longitudinal data on disease progression. Utilizing this cohort, we have identified
several potential biomarkers and clinical outcome assessments (COAs) that reflect the core CCHS phenotype
and could be measured remotely, in the local hospital setting or in the homes of CCHS patients, without
need for travel to a CCHS referral center. With this R03 application we propose to leverage this singular data
set to validate the psychometric properties of these biomarkers and COAs by establishing their rest-retest
reliability, sensitivity, longitudinal stability and clinical validity as compared to gold-standard assessments. The
overall aim is to e...

## Key facts

- **NIH application ID:** 10514295
- **Project number:** 1R03TR003869-01A1
- **Recipient organization:** LURIE CHILDREN'S HOSPITAL OF CHICAGO
- **Principal Investigator:** DEBRA ELLYN WEESE-MAYER
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $77,500
- **Award type:** 1
- **Project period:** 2022-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10514295

## Citation

> US National Institutes of Health, RePORTER application 10514295, PHOX2B Congenital Central Hypoventilation Syndrome (CCHS) Physiologic Signatures in Readiness for Future Clinical Trials (1R03TR003869-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10514295. Licensed CC0.

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