Gene Therapy for Huntington’s Disease: The Final Strategy for a Cure?

Huntington’s disease (HD) has become a target of the first clinical trials for gene therapy among movement disorders with a genetic origin. More than 100 clinical trials regarding HD have been tried, but all failed, although there were some improvements limited to symptomatic support. Compared to other neurogenetic disorders, HD is known to have a single genetic target. Thus, this is an advantage and its cure is more feasible than any other movement disorder with heterogeneous genetic causes. In this review paper, the authors attempt to cover the characteristics of HD itself while providing an overview of the gene transfer methods currently being researched, and will introduce an experimental trial with a preclinical model of HD followed by an update on the ongoing clinical trials for patients with HD.

Differences in Associated Factors according to the Time of Occurrence of Pressure Ulcers in Intensive Care Unit Patients / 중환자간호학회지

Purpose@#: This study aimed to present the incidence of pressure ulcers and identify different associated factors according to the time of occurrence of pressure ulcers in intensive care unit (ICU) patients. @*Methods@#: The participants were 313 patients who reported pressure ulcers among 2,908 patients in ICUs at a large tertiary hospital in Gyeonggi-do. Among them, 220 patients (70.3%) had a pressure ulcer before admission, and 93 patients (29.7%) reported newly developed pressure ulcers after admission to the ICU. Data were collected between August 2018 and April 2019. Along with the time of occurrence and characteristics of pressure ulcers, diverse associated factors were gathered through electronic medical records. Data were analyzed using descriptive statistics, independent t-tests, and χ2-tests. @*Results@#: Different risk factors associated with pressure ulcers in ICU patients according to the time of occurrence were main diagnosis, score of acute physiology and chronic health evaluation, score of Richmond agitation sedation scale, level of consciousness, administered sedatives, use of a ventilator, insertion of a feeding tube, and the duration of fasting period. @*Conclusion@#: Based on the results of this study, healthcare providers, especially ICU nurses, should try to detect early signs and symptoms of pressure ulcers, taking into account the derived factors associated with pressure ulcers in ICU patients. Practical intervention programs and strategies considering the factors associated with pressure ulcers must be developed to prevent and alleviate such ulcers in ICU patients in the future.

Exosome-Based Delivery of miR-124 in a Huntington's Disease Model

OBJECTIVE: Huntington's disease (HD) is a genetic neurodegenerative disease that is caused by abnormal CAG expansion. Altered microRNA (miRNA) expression also causes abnormal gene regulation in this neurodegenerative disease. The delivery of abnormally downregulated miRNAs might restore normal gene regulation and have a therapeutic effect. METHODS: We developed an exosome-based delivery method to treat this neurodegenerative disease. miR-124, one of the key miRNAs that is repressed in HD, was stably overexpressed in a stable cell line. Exosomes were then harvested from these cells using an optimized protocol. The exosomes (Exo-124) exhibited a high level of miR-124 expression and were taken up by recipient cells. RESULTS: When Exo-124 was injected into the striatum of R6/2 transgenic HD mice, expression of the target gene, RE1-Silencing Transcription Factor, was reduced. However, Exo-124 treatment did not produce significant behavioral improvement. CONCLUSION: This study serves as a proof of concept for exosome-based delivery of miRNA in neurodegenerative diseases.

Insulin resistance is associated with new-onset cardiovascular events in nondiabetic patients undergoing peritoneal dialysis

BACKGROUND: Chronic exposure to high glucose-containing peritoneal dialysis solution and consequent abdominal obesity are potential sources of insulin resistance in patients requiring prevalent peritoneal dialysis. The aim of this study was to elucidate the prognostic values of insulin resistance on new-onset cardiovascular events in nondiabetic patients undergoing prevalent peritoneal dialysis. METHODS: A total of 201 nondiabetic patients undergoing prevalent peritoneal dialysis were recruited. Insulin resistance was assessed by homeostatic model assessment of insulin resistance (HOMA-IR). The primary outcome was new-onset cardiovascular events during the follow-up period. Cox proportional hazard analysis was performed to ascertain the independent prognostic value of HOMA-IR for the primary outcome. RESULTS: The mean age was 53.1 years and male was 49.3% (n=99). The mean HOMA-IR was 2.6+/-2.1. In multivariate linear regression, body mass index (beta=0.169, P=0.011), triglyceride level (beta=0.331, P<0.001), and previous cardiovascular diseases (beta=0.137, P=0.029) were still significantly associated with HOMA-IR. During a mean follow-up duration of 36.8+/-16.2 months, the primary outcome was observed in 36 patients (17.9%). When patients were divided into tertiles according to HOMA-IR, the highest tertile group showed a significantly higher incidence rate for new-onset cardiovascular events compared to the lower two tertile groups (P=0.029). Furthermore, multivariate Cox analysis revealed that HOMA-IR was an independent predictor of the primary outcome (hazard ratio=1.18, 95% confidence interval=1.03-1.35, P=0.014). CONCLUSION: Insulin resistance measured by HOMA-IR was an independent risk factor for new-onset cardiovascular events in nondiabetic patients undergoing prevalent peritoneal dialysis.