Background:Huntington’s disease (HD) is an inherited neurodegenerative disease and is characterized by atrophy of certain regions of the brain in a progressive manner. HD patients experience behavioral changes and uncontrolled movements which can be primarily attributed to the atrophy of striatal neurons. Previous publications describe the models of the HD striatum using induced pluripotent stem cells (iPSCs) derived from HD patients with a juvenile onset (JHD). In this model, the JHD iPSC-derived striatal cultures had altered neurodevelopment and contained a high number of nestin expressing progenitor cells at 42 days of differentiation.Objective:To further characterize the altered neurodevelopmental phenotype and evaluate potential phenotypic reversal.Methods:Differentiation of human iPSCs towards striatal fate and characterization by means of immunocytochemistry and stereological quantification.Results:Here this study demonstrates a distinct delay in the differentiation of the JHD neural progenitor population. However, reduction of the JHD aberrant progenitor populations can be accomplished either by targeting the canonical Notch signaling pathway or by treatment with HTT antisense oligonucleotides (ASOs).Conclusions:In summary, this data is postulated to reflect a potential overall developmental delay in JHD.

Prescribing a ketogenic diet (KD) is a century-old dietary intervention mainly used in the context of intractable epilepsy. The classic KD and its variants regained popularity in recent decades, and they are considered potentially beneficial in a variety of neurological conditions other than epilepsy. Many patients with multiple sclerosis have attempted diet modification for better control of their disease, whereas evidence thus far remains insufficient to recommend a specific diet for these patients. The results of three pilot clinical trials of KD therapy for multiple sclerosis, as well as several related studies, have been reported in recent years. The preliminary findings suggest that KD is safe, feasible, and potentially neuroprotective and disease-modifying for patients with multiple sclerosis. Research on corresponding rodent models also lent support to the efficacy of KD in the prevention and treatment of experimental autoimmune encephalomyelitis and toxin-induced inflammatory demyelinating condition in the brain. Furthermore, the animal studies yielded mechanistic insights into the molecular mechanisms of KD action in relevant situations, paving the way for precision nutrition. Herein we review and synthesize recent advances and also identify unresolved issues, such as the roles of adipokines and gut microbiota, in this field. Hopefully this panoramic view of current understanding could inform future research directions and clinical practice with regard to KD in MS and related conditions.

Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease with a five-year survival rate of around 7% due to its late diagnosis, rapid metastasis, and chemotherapy resistance. For a small proportion (10-20%) of early-stage patients however, surgical resection of the pancreatic tumor offers the best chance for survival (5-year rate of 20%). Given the clinical challenges and the need for personalized care strategies to maximize patient survival, we propose the utility of the minimally invasive liquid biopsy to identify circulating biomarkers in patient blood to guide prognosis and monitor treatment. This study used the non-enriching third generation High-Definition Single Cell Assay (HDSCA3.0) workflow to investigate the clinical significance of a heterogeneous circulating rare cell population in both the peripheral and portal vein blood of early-stage PDAC patients (n = 20) at four different time points—pre-, during, and post- surgical resection, as well as at one-week follow-up. Compared to normal donor samples (n = 50), PDAC patients had a significantly greater incidence of circulating tumor cells (CTCs: cytokeratin-positive (CK+) and CD35/45-negative). There was no significant difference in rare cell incidence between peripheral and portal vein samples. However, specific phenotypes of rare cells were observed at different frequencies based on time of sample collection. Patient samples collected pre-surgery had a significantly higher incidence of CTCs than samples collected during surgery, while post-surgery samples had a significantly higher incidence of total CK+ rare cells and mesenchymal CTCs (Vimentin-positive, CK+) than during-surgery samples. While post-surgical samples also had a higher total CK+ rare cell and CTC incidence than pre-surgical samples, the difference was not statistically significant. Additionally, patients who received neoadjuvant therapy with surgical resection had lower average incidence of rare cells. Overall, the data presented here reveal that 1) liquid biopsy analytes are detected at a higher incidence in localized PDAC than normal donors; 2) the time point of sample collection in relation to surgery leads to a statistically significant different in frequency of detectable analytes; and 3) anatomical location of blood draw is not associated with difference in rare cell incidence. This study demonstrates the liquid biopsy’s utility in early-stage PDAC detection at the time of surgical resection. Citation Format: Emmeline Y. Lin, George Courcoubetis, Divya Suresh, Jeremy Mason, Stephen J. Pandol, Simon Lo, Nicholas Nissen, Srinivas Gaddam, Peter Kuhn, Stephanie N. Shishido. Liquid biopsy to detect biomarkers in early-stage surgically-resected pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3320.