👤 Chelsea L Faber

Spinocerebellar ataxia type 3 (SCA3) is one of the most common dominantly inherited ataxias worldwide. Despite research advances, no approved disease-modifying treatment exists, and management focuses on symptom alleviation and functional capacity maximization. Symptomatic treatment guidelines are scarce, leaving decisions to physicians' discretion. The lack of studies on SCA3 symptom management hinders therapy standardization. The aim of this study was to investigate medication-usage patterns among SCA3 mutation carriers and controls included in the multicentric European Spinocerebellar Ataxia Type-3/Machado-Joseph Disease Initiative (ESMI) cohort. We conducted a retrospective cross-sectional analysis of the medication taken by ESMI participants enrolled in the study between 2016 and 2023. Medication being used at the most recent follow-up visit available was categorized according to the Anatomical Therapeutic Chemical system. Comparisons between groups were performed using nonparametric tests for continuous variables and Fisher's exact test for categorical variables. In addition, a retrospective longitudinal analysis was conducted to study the impact of medication subclasses on disease progression, using linear mixed-effects models adjusted for relevant covariates. A total of 474 participants were included, comprising 344 SCA3 mutation carriers and 130 controls. Compared with controls, SCA3 subjects took more vitamins, mineral supplements, muscle relaxants, and medications targeting the nervous system. Psychoanaleptics and vitamins were introduced early in the disease course, whereas most other subclasses were initiated in mid-to-late stages, coinciding with the onset of neurological symptoms. Substantial disparities in medication usage were observed across the study centers. None of the medication subclasses commonly used by patients with SCA3 showed a significant impact on disease progression. This is the first study to explore medication usage patterns in SCA3 mutation carriers. Our study provides a comprehensive overview of the medications administered in SCA3 and underscores the importance of collaborative efforts toward achieving standardized clinical practices in the management of this disease. Show less

In rodent models of type 2 diabetes (T2D), sustained remission of hyperglycemia can be induced by a single intracerebroventricular (icv) injection of fibroblast growth factor 1 (FGF1), and the mediobasal hypothalamus (MBH) was recently implicated as the brain area responsible for this effect. To better understand the cellular response to FGF1 in the MBH, we sequenced >79,000 single-cell transcriptomes from the hypothalamus of diabetic Lep Show less

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease (1/500) and the most common cause of sudden cardiac death in young people. Pathogenic mutation detection of HCM is having a growing impact on the medical management of patients and their families. However, the remarkable genetic and allelic heterogeneity makes molecular analysis by conventional methods very time-consuming, expensive and difficult to realise in a routine diagnostic molecular laboratory. The authors used their custom DNA resequencing array which interrogates all possible single-nucleotide variants on both strands of all exons (n=160), splice sites and 5'-untranslated region of 12 HCM genes (27 000 nucleotides). The results for 122 unrelated patients with HCM are presented. Thirty-three known or novel potentially pathogenic heterozygous single-nucleotide variants were identified in 38 patients (31%) in genes MYH7, MYBPC3, TNNT2, TNNI3, TPM1, MYL3 and ACTC1. Although next-generation sequencing will replace all large-scale sequencing platforms for inherited cardiac disorders in the near future, this HCM resequencing array is currently the most rapid, cost-effective and reasonably efficient technology for first-tier mutation screening of HCM in clinical practice. Because of its design, the array is also an appropriate tool for initial screening of other inherited forms of cardiomyopathy. Show less