Implications of Epigenetic Regulation in Congenital Myotonic Dystrophy through Development
NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development
About This Grant
Project Summary Congenital myotonic dystrophy (CDM), the most severe form of myotonic dystrophy, causes muscle weakness, breathing problems, and feeding difficulties at birth. During childhood affected individuals experience intellectual impairment and gastrointestinal issues while, in contrast, muscle strength and weakness improve. Muscle symptoms experienced by adults with myotonic dystrophy, including myotonia and fatigue, are not observed until individuals reach adolescence. Individuals with CDM and myotonic dystrophy type 1 (DM1) both exhibit widespread alternative splicing dysregulation due to the sequestration of muscleblind-like (MBNL) proteins by expanded CUG-repeat DMPK RNA. Our Center previously performed RNA sequencing on 43 congenital myotonic dystrophy muscle biopsies from individuals 2 weeks to 16 years of age. We found that the severity of RNA mis- splicing mirrored the triphasic course of muscle symptoms captured clinically; children in early childhood showed improvement in RNA splicing dysregulation that regressed in adolescence. Preliminary data also indicates varying DMPK expression in CDM patients, suggesting DMPK’s potential role in CDM pathophysiology, particularly in infancy. While these observations correlate with the clinical course of CDM, the mechanisms responsible for these dynamic shifts remain unknown. This proposal is designed to further clarify and define the molecular mechanisms responsible for the clinical and molecular progression of CDM. This study will characterize the epigenetic landscape around the DMPK locus in skeletal muscle across CDM development and elucidate how DMPK methylation contributes to CDM. We hypothesize that epigenetic modifiers play a significant role in the unique clinical/molecular pattern we observe in individuals with CDM across development, most specifically in infancy, by serving as a protective mechanism to modulate toxic DMPK expression via changes in methylation. Aim 1 will characterize methylation patterns in matched skeletal muscle and blood samples from CDM children, adult DM1 patients, and controls, analyzing changes across development and disease progression. Aim 2 will assess the role of DMPK methylation using iPSCs and CRISPR-based systems to modulate methylation and MBNL expression, examining the molecular effects in myogenic cells. At the completion of this project, we will have mapped the epigenomic course of CDM disease progression across pediatric development and performed experiments vital to understanding the unique mechanisms that contribute to CDM. This research will enhance understanding of CDM's clinical and molecular progression, identify potential biomarkers for therapeutic trials, and provide insights into targeting DMPK methylation in CDM.
Grant Summary
Implications of Epigenetic Regulation in Congenital Myotonic Dystrophy through Development is a NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development grant providing up to $46K for university, nonprofit, healthcare org. Applications are due 2029-12-04 (open). Check eligibility and apply with FindGrants.
Focus Areas
Eligibility
How to Apply
Up to $46K
2029-12-04
- 1Confirm your organization is eligible for Implications of Epigenetic Regulation in Congenital Myotonic Dystrophy through Development from NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development, checking organization type, location, and any population or project requirements.
- 2Gather the required documents and information, including your organization details, project plan, and budget figures.
- 3Draft your application narrative and budget addressing the funder's priorities and review criteria. FindGrants can draft each section for you to review and edit.
- 4Review every section against the requirements checklist, then export a submission-ready application pack and submit it to NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development before the deadline.
Don't want to draft it yourself?
We'll draft the complete application against NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development's requirements, run a quality review, and email you a submission-ready PDF plus an editable Word doc within 5 business days. Most orders deliver in 24-48 hours. Flat $399, any grant size.
AI Requirement Analysis
Detailed requirements not yet analyzed
Have the NOFO? Paste it below for AI-powered requirement analysis.
Implications of Epigenetic Regulation in Congenital Myotonic Dystrophy through Development: Frequently Asked Questions
Who is eligible for the Implications of Epigenetic Regulation in Congenital Myotonic Dystrophy through Development?
Implications of Epigenetic Regulation in Congenital Myotonic Dystrophy through Development is offered by NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
How much funding does the Implications of Epigenetic Regulation in Congenital Myotonic Dystrophy through Development provide?
Implications of Epigenetic Regulation in Congenital Myotonic Dystrophy through Development provides up to $46K per award from NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the Implications of Epigenetic Regulation in Congenital Myotonic Dystrophy through Development deadline?
Applications for Implications of Epigenetic Regulation in Congenital Myotonic Dystrophy through Development are due 2029-12-04 (open). Because deadlines can change, verify the date with the funder, NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the Implications of Epigenetic Regulation in Congenital Myotonic Dystrophy through Development?
To apply for Implications of Epigenetic Regulation in Congenital Myotonic Dystrophy through Development, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development.