2015 Helen Walker Research Grant Award
National Institutes of Health (NIH) | Nina Raben, MD, PhD, & Rosa Puertollano, PhDSupporting research exploring curcumin as a complementary therapeutic strategy for Pompe disease.
Quick Facts
Year Awarded:
2015
Funding Amount:
$140,000
Lead Investigators:
Nina Raben, MD, PhD; Rosa Puertollano, PhD
Institution:
National Institutes of Health (NIH)
Research Focus:
Therapeutic development and ERT optimization
Status:
Completed
Project Title
Curcumin: Can it promote cellular clearance in Pompe disease?
Project Snapshot
In 2015, the AMDA awarded the Helen Walker Research Grant to Nina Raben, MD, PhD, and colleagues at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and the National Heart, Lung, and Blood Institute (NHLBI) at the National Institutes of Health, to support a project exploring curcumin as a complementary therapeutic strategy for Pompe disease. The goal of the project was to determine whether this natural compound, derived from the spice turmeric, could activate a transcription factor called TFE3 to promote cellular clearance — addressing not only the primary enzyme deficiency but also the secondary cellular abnormalities that enzyme replacement therapy alone cannot resolve.
The team used both diseased cultured muscle cells and Pompe mouse models to test the effects of curcumin on lysosomal exocytosis, autophagic buildup, mitochondrial function, and calcium regulation. Preliminary studies had already shown that curcumin could stimulate TFE3 activation and promote the removal of accumulated lysosomal material from Pompe muscle cells. Beyond its potential to clear cellular debris, curcumin was also expected to help address muscle atrophy — a persistent feature of Pompe disease — making it a candidate for use alongside existing enzyme replacement treatment.
Research Objectives
The project aimed to address several key questions related to treatment outcomes in Pompe disease:
1. Evaluate the therapeutic efficacy of curcumin in mouse models of Pompe disease
Researchers proposed feeding curcumin to Pompe disease mouse models to determine whether the compound could improve muscle pathology and overall physical performance. The study examined effects on glycogen accumulation, lysosomal size, autophagic buildup, mitochondrial function, calcium regulation, muscle strength, and endurance in treated animals.
2. Determine the molecular mechanism of curcumin-mediated activation of TFE3 in muscle cells
The research team planned to investigate how curcumin activates the transcription factor TFE3 and promotes lysosomal exocytosis in Pompe muscle cells. Using cultured GAA-deficient myotubes, the study aimed to identify signaling pathways involved in TFE3 activation and map the gene networks responsible for lysosomal and autophagic biogenesis.
Why This Matters
Pompe disease is characterized not only by glycogen accumulation but also by secondary cellular abnormalities that interfere with normal muscle function. These include defective autophagyThe cell's internal cleanup system that removes damaged or unneeded material. More, abnormal mitochondria, and disrupted calcium regulation.
By targeting cellular clearance pathways through activation of the transcription factor TFE3, this research aimed to address both the primary and secondary pathological processes in Pompe disease. If successful, curcumin — or related compounds that activate the same pathway — could potentially serve as a complementary therapy alongside enzyme replacement treatment.
Research Team
Institution
National Institutes of Health, United States
Lead Investigator
Nina Raben, MD, PhD
Staff Scientist, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), NIH
Collaborator
Rosa Puertollano, PhD
Senior Investigator, National Heart, Lung, and Blood Institute (NHLBI), NIH
Research Staff
Lishu Li, PhD – Research Fellow
Jeong-A Lim, PhD – Postdoctoral Fellow
Lead Investigator
Nina Raben, MD, PhD
Staff Scientist, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), NIH
Collaborator
Rosa Puertollano, PhD
Senior Investigator, National Heart, Lung, and Blood Institute (NHLBI), NIH
Research Staff
Lishu Li, PhD – Research Fellow
Jeong-A Lim, PhD – Postdoctoral Fellow
Grant Support
The AMDA awarded $140,000 through the Helen Walker Research Grant to support this project.
Funding supported research personnel, laboratory reagents for cell culture experiments, maintenance of Pompe disease mouse models, behavioral and physiological testing of animals, and analysis of muscle tissue and cellular pathways involved in lysosomal clearance.
Publications Resulting from This Research
This section will be updated as we collect more information about publications resulting from this research.
Related Outputs
This section will be updated as we collect more information about presentations, follow-up studies, or related outputs from this project.
Ongoing Impact
Research supported by the Helen Walker Research Grant helps build knowledge that can shape future studies, clinical care, and treatment strategies in Pompe disease. As additional publications, presentations, and follow-up work emerge, this page will continue to be updated.
About the Helen Walker Research Grant
The Helen Walker Research Grant honors Helen Walker, a dedicated patient advocate and leader in the Pompe community. Through this grant, the AMDA supports innovative research aimed at improving understanding, treatment, and care for individuals living with Pompe disease.
Explore more Helen Walker Research Grant awardees and the growing body of Pompe research supported by the AMDA.