# Brain Structure and Clinical Endpoints in Myotonic Dystrophy Type 2-

> **NIH NIH K23** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2024 · $41,764

## Abstract

Project Summary
This administrative supplement application seeks funding to expand the research objectives for the current
award, entitled “Brain Structure and Clinical Endpoint in Myotonic Dystrophy Type 2” (K23 NS125110). The
parent K23 award aims to evaluate the relationship between brain structure and function on cognition and
motor performance in adults with myotonic dystrophy type 2 (DM2). The proposed supplement will support a
DM2 biofluid repository initiative and collection of additional Alzheimer’s Disease (AD) biomarkers to sufficiently
address potential confounders from age-related comorbidities. DM2, a multisystemic disorder, results from a
CCTG repeat expansion in the CNBP gene, where the RNA gain-of-function is the main disease mechanism.
Although muscle weakness is the key feature in DM2, almost 70% of patients report that impaired cognition is
one of the most disabling symptoms, adversely affecting their quality of life. A sparse literature describes
cognitive deficits in executive function, attention, verbal memory, and processing speed in those with DM2. Yet
the mechanisms that lead to cognitive impairment in DM2 are poorly understood as brain imaging studies are
very limited. Nevertheless, most studies suggest that, compared to controls, DM2 primarily affects white matter
(WM), with reduced cerebral WM volume and impaired WM integrity derived from diffusion tensor imaging
(DTI). Emerging evidence has identified tau mis-splicing and tangle pathology in the brains of those with DM2,
which has prompted interest in elucidating the role of tau in DM2-related cognitive impairment. One method of
investigating central nervous system (CNS) mechanisms is to evaluate fluid biomarkers that reflect brain
pathology. But no studies to date have meticulously evaluated brain structure and their relationships to clinical
endpoints and biomarkers of CNS pathology in DM2. In Aim 1, I will evaluate brain morphometry and DTI
measures of WM integrity, including fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD)
in 40 adults with DM2 vs. 40 age and sex-matched control. In Aim 2, I will determine relationships between
measures of WM integrity (FA and RD) and clinical (cognitive and motor) endpoints. In Aim 3, I will conduct a
pilot proof-of-concept study to characterize tau profiles in the plasma and CSF of DM2 and associate these
findings with measures of brain structure and cognitive endpoints. The original study did not adequately
address potential confounders from age-related comorbidities, i.e., preclinical AD. The requested funds will
enable me to examine plasma β-amyloid biomarkers (Aβ42, Aβ40) to help mitigate this concern. The
supplement will also establish a DM2 biofluid repository at the Biospecimen Exchange for Neurological
Disorders (BioSEND). By utilizing BioSEND’s infrastructure, this initiative will ensure the long-term preservation
of samples, foster collaborations, and facilitate access for the broader re...

## Key facts

- **NIH application ID:** 11116011
- **Project number:** 3K23NS125110-03S1
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Araya Puwanant
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $41,764
- **Award type:** 3
- **Project period:** 2022-07-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11116011

## Citation

> US National Institutes of Health, RePORTER application 11116011, Brain Structure and Clinical Endpoints in Myotonic Dystrophy Type 2- (3K23NS125110-03S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11116011. Licensed CC0.

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