# Intervention Strategies for Non-Folate Responsive Neural Tube Defects

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2024 · $627,670

## Abstract

ABSTRACT
Congenital defects are the leading cause of neonatal mortality, resulting in more infant deaths than the combined
adult death tolls of Alzheimer’s disease, strokes, diabetes, and influenza. Neural tube defects (NTDs), the second
most common category of human birth defects, arise when the neural tube fails to close properly during
neurulation. Globally, these defects are estimated to affect approximately 18.6 per 10,000 live births and the
prevalence of NTDs is 1–2 per 1,000 births in most regions of the US. There are approximately 2,300 NTD-
affected pregnancies in the US each year, whose lifetime medical costs are estimated to be $560,000 per child
or $1.68 billion per year nationwide. Despite intensive investigation for decades, relatively little is known about
the underlying NTD risk factors. It is generally accepted that NTDs are of a multi-factorial origin, having both
environmental and genetic factors that contribute to the malformation. Although it is established that
periconceptional use of folic acid (FA) prevents a significant percentage of the population burden of NTDs, the
mechanisms underlying those processes by which FA reduces NTD risk remains unknown. Importantly, there
are significant numbers of NTDs that are not preventable by FA supplementation, with these FA-resistant NTDs
occurring at an apparent baseline rate of 5 per 10,000 live births. Thus, NTDs remain a substantial public health
problem, and there is a critical need to understand the mechanisms underlying FA-resistant NTDs and to
develop novel intervention strategies targeting this population
To expand upon work performed in the initial funding period, our proposed line of study explores mechanisms
by which impairment of mitochondrial one carbon metabolism causes NTDs and how our proposed interventions
successfully restore proper NTC. Simultaneously, we are testing the efficacy and investigating mechanisms by
which glycine supplementation rescues these FA-resistant defects. Establishing these mechanisms and relating
them to actual human NTD variants may eventually allow us to utilize our proposed intervention strategies to
prevent previously unpreventable birth defects by informing public health policy or precision medicine strategies,
thus reducing the significant negative health burden of these debilitating defects on affected families and the
public.

## Key facts

- **NIH application ID:** 10892648
- **Project number:** 5R01HD083809-10
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** RICHARD H. FINNELL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $627,670
- **Award type:** 5
- **Project period:** 2016-02-15 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10892648

## Citation

> US National Institutes of Health, RePORTER application 10892648, Intervention Strategies for Non-Folate Responsive Neural Tube Defects (5R01HD083809-10). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10892648. Licensed CC0.

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