# Calcium Dysregulation and Cell Function in Spinal Muscular Atrophy

> **NIH NIH R01** · HENRY M. JACKSON FDN FOR THE ADV MIL/MED · 2021 · $381,240

## Abstract

PROJECT SUMMARY/ABSTRACT
Spinal muscular atrophy (SMA) is one of the most common inherited cause of death in infants
and young children. SMA is caused by the deletion or mutation in the survival of motor neuron 1
(SMN1) gene, leading to a deficiency of the ubiquitously expressed SMN protein. Recent
approved therapies increase SMN protein and partially correct the motor neuron loss and
muscle degeneration that are hallmarks of the disease. However, SMA patients require critical
care as a result of cardiopulmonary impairment and opportunistic infections. This observation,
together with extensive new preliminary data, leads us to hypothesize that SMN-deficiency
impairs cardiomyocyte function, representing a previously unrecognized contribution of the
cardiovascular system on SMA disease pathology. To test this hypothesis, we will use primary
cardiomyocytes from a mouse model of the disease and human cardiomyocytes derived from
SMA patient induced pluripotent stem cells (iPSC) to determine the consequences of SMN
deficiency on contractile function (Aim 1), the molecular mechanisms leading to impaired
contraction (Aim 2), and characterize cardiovascular deficiencies following SMN restoration in
SMA mice (Aim 3). The preliminary results using our unique approach are already providing
novel mechanistic insight into a poorly understood aspect of the SMA disease process which
could be critically important when designing strategies to manage the disease clinically.

## Key facts

- **NIH application ID:** 10100087
- **Project number:** 1R01NS119594-01
- **Recipient organization:** HENRY M. JACKSON FDN FOR THE ADV MIL/MED
- **Principal Investigator:** Barrington G Burnett
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $381,240
- **Award type:** 1
- **Project period:** 2021-01-20 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10100087

## Citation

> US National Institutes of Health, RePORTER application 10100087, Calcium Dysregulation and Cell Function in Spinal Muscular Atrophy (1R01NS119594-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10100087. Licensed CC0.

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