Duke Neurology Research Round Up, March 2023

By William Alexander

 The shortest month of the year was still an active one for research in the Duke Neurology Department. Our faculty, trainees, and staff members contributed to 10 new peer-reviewed journal articles this February. Highlights include a new Neurology study linking the neighborhood quality with health outcomes for neurological conditions, a pilot study that identified small retinal changes as a potential biomarker for Alzheimer's disease and other conditions, and an analysis of more than 20 years of data from our Myasthenia Gravis Clinic Registry that measured how trends in treatment have led to improved outcomes. Read about these and other recent publications, and find links to the original research articles themselves, in the paragraphs below.

Hospital Neurology

  • Living in neighborhoods with higher poverty levels and fewer educational and employment opportunities is associated with an increased risk of hospitalization for stroke, epilepsy, according to a new Neurology article by Matt Luedke, MD, Jay Lusk, and colleagues from across the Duke University School of Medicine. Their analysis found that living in a poorer neighborhood was strongly associated with 30-day mortality for many common neurological conditions even after accounting for baseline comorbidity burden and individual socioeconomic status. Read that article here. 

Memory Disorders

  • In the future, small changes to the vasculature of the retina may be an early, noninvasive  biomarker of Alzheimer’s disease and other forms of neurodegeneration. Kim Johnson, MD, and Andy Liu, MD, MS, were part of a team that assessed the presence of these abnormalities in dementia from Alzheimer’s and mild cognitive impairment using ultra-widefield retinal imaging. Their pilot study found statistically significant differences in the retinal vasculature in peripheral regions of the retina among the distinct cognitive stages. Read their full study in Translational Vision Science & Technology.

Neurodegeneration and Neurotherapeutics

  • A new article by K. Matthew Scaglione, PhD, and colleagues may lay the groundwork for new potential treatments for Huntington’s disease and other conditions. The slime mold Dictyostelium discoideum has a natural resistance to the process of polyglutamine aggregation which is responsible for these conditions. Scaglione and colleagues’ previous research had identified serine-rich chaperone protein 1 (SRCP1) as a protein that suppresses polyglutamine aggregation in Dictyostelium and human cells. In this article, they determined that SRCP1 inhibits secondary nucleation in a manner dependent upon the regions flanking the polyglutamine tract and confirmed that it was sufficient to inhibit aggregation of polyglutamine-expanded ataxin-3. Read that article in ACS Chemical Biology.

Neuromuscular Disease

  • The Duke Myasthenia Gravis (MG) Clinic Registry contains comprehensive physician-derived data on patients with MG seen at Duke since 1980. Janice Massey, MD, and Don Sanders, MD, were the senior authors of a new study that examines more than two decades of that data. Massey, Sanders, as well as Lisa Hobson-Webb, MD, Michael Lutz, PhD, Shruti Raja, MD, and Vern Juel, MD performed a retrospective cohort study of myasthenia gravis patients recorded in the registry since 2000. Their analysis found that 72 percent of patients seen achieved treatment goals while also demonstrating the added value of treatment modalities developed since 2018. Read the full article in Muscle and Nerve.
  • Rick Bedlack, MD, PhD, was the senior author of a study that sheds light into the role cerebrospinal fluid (CSF) plays in the development of amyotrophic lateral sclerosis (ALS). Bedlack and colleagues filtered CSF  from 11 ALS patients and then injected groups of mice with saline, filtered ALS-CSF, or unfiltered ALS-CSF. They then identified proteins implicated in ALS pathogenesis, showed that filtration reduced those proteins, and found that mice receiving them had reduced mobility, demonstrating that CSF filtration these were removed in significant amounts could be a novel solution for patients suffering from this deadly and irreversible condition. Read the full article in Cureus

Stroke and Vascular Neurology

  • Senior author Brian Mac Grory, MB BCh, MRCP, and Emily O’Brien, PhD, contributed to a new study examining the relationship between atrial fibrillation (AF), a cardiac arrhythmia that underlies over 25% of cerebral ischemic strokes, and central retinal artery occlusion (CRAO), also referred to as eye strokes. The team’s analysis of nearly 3 million patients with hospital documented AF found an inverse relationship between AF and risk of CRAO. Read their findings and discussion in the latest issue of Stroke.

Translational Brain Sciences

  • OnabotulinumtoxinA (onabotA) is approved globally for prevention of chronic migraine, but the way this medication actually functions has not been fully understood. Carlene Moore, PhD, and Ashley Moore, MAT, were the senior authors of a new article that deepen our understanding of the sensory mechanism of action of this medication and supports the notion that, once endocytosed, the cytosolic light chain of onabotulinumtoxinA cleaves synaptosomal-associated protein-25 kDa to prevent soluble N-ethylmaleimide-sensitive factor attachment protein receptor-mediated processes more generally in motor, autonomic, and sensory neurons. The Moore lab’s Lily Orta, Emma Xiong, Gene Moon, Shinbe Choi, and Christopher Wickware also contributed to the article, which appears in the latest issue of Cephalagia. Read it here.
  • Simon Gregory, PhD, was the senior author of a study that broadens our understanding of the factors that influence oxytocin levels in the blood as well as how oxytocin affects people living with autism. Their team investigated whether genetic and epigenetic factors contribute to variable oxytocin levels in the blood in individuals with autism spectrum disorder. Their analysis identified genetic associations with plasma oxytocin, several of which reside in known autism risk genes. Read the full study in Autism Research.
  • Simon Gregory, PhD, also contributed to a new article that advances our understanding of the deleterious effects of aging and obesity on the human body. Gregory and colleagues identified a subset of genes with critical roles in progenitors and in diseases of obesity and aging. The team also identified candidate driver genes that appeared recurrently in all analyses and comparisons undertaken. Read the full study in FASEB Journal.
  • Microporous annealed particle scaffolds (MAPS) are a new class of granular materials generated through the interlinking of tunable microgels, which produce an interconnected network of void space. Tatiana Segura, PhD, was the senior author of a new study that investigates  the immunomodulatory effect of D-amino acid MAPS in a subcutaneous implantation model. Read that article in Advanced Science.