# Investigation of Cardiac Arrhythmias in TANGO2 Disorder

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2024 · $800,951

## Abstract

ABSTRACT
 TANGO2 Deficiency Disorder is an autosomal recessive disease caused by genetic alterations in
TANGO2 (Transport and Golgi Organization Homolog 2). Patients, primarily young children, with TANGO2
disorder are susceptible to recurring episodes of metabolic crisis and life-threatening ventricular arrhythmias that
lead to cardiac arrest and death. TDD is associated with a high mortality because TDD-related arrhythmias do
not respond to standard antiarrhythmic therapy. Promising new data from an international patient registry and
natural history study has demonstrated B-vitamin supplementation prevents and may treat arrhythmias but the
mechanism by which they work remain unclear. In addition, despite investigations, the exact functional role of
TANGO2 protein remains unknown. We believe that current therapeutic interventions are ineffective because
we lack an understanding of the pathophysiologic mechanisms driving TANGO2-related arrhythmia development
and by studying the role of B-vitamins in arrhythmia prevention and treatment will provide answers.
 We propose a study to evaluate vitamin B9, a component of B-vitamins that has shown effective
suppression of ventricular arrhythmias based on preliminary data. This study is a translational study, combining
human patients, cellular and animal models. Specifically, we will utilize TDD patients in an existing natural history
study, Tango2 -/- mouse model, and TANGO2 deficienct induced pluripotent stem cell cardiomyocytes (iPSC-
CMs) to study the effects of folate on ventricular arrhythmia development and to determine the mechanism
driving ventricular arrhythmias in TDD. Our study will provide clinically relevant data and novel insights into the
pathophysiologic mechanisms driving TDD-arrhythmia development and help improve patient survival and
outcomes in TANGO2 disorder.

## Key facts

- **NIH application ID:** 10981534
- **Project number:** 1R01HL166388-01A1
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Christina Yumi Miyake
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $800,951
- **Award type:** 1
- **Project period:** 2024-08-09 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10981534

## Citation

> US National Institutes of Health, RePORTER application 10981534, Investigation of Cardiac Arrhythmias in TANGO2 Disorder (1R01HL166388-01A1). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10981534. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*