Effects of Trehalose Administration in Patients with Mucopolysaccharidosis Type III.

BACKGROUND AND AIM: Mucopolysaccharidosis type III (MPS III) is a rare autosomal recessive lysosomal storage disease (LSD) caused by a deficiency of lysosomal enzymes required for the catabolism of glycosaminoglycans (GAGs), mainly in the central nervous system. Trehalose has been proposed as a potential therapeutic agent to attenuate neuropathology in MPS III. We conducted a single-arm, open-label study to evaluate the efficacy of trehalose treatment in patients with MPS IIIA and MPS IIIB. METHODS: Five patients with MPS III were enrolled. Trehalose was administrated intravenously (15 g/week) for 12 weeks. Health-related quality of life and cognitive function, serum biomarkers, liver, spleen, and lung imaging were assessed to evaluate trehalose efficacy at baseline and trial end (week 12). RESULTS: TNO-AZL Preschool children Quality of Life (TAPQOL) scores increased in all patients, and the mean scores for quality of life were increased after the intervention. Serum GAG levels were reduced in all treated patients (however, the differences were not statistically significant). Alanine aminotransferase (ALT) levels were reduced in all patients post-treatment (p=0.0039). The mean levels of aspartate transaminase (AST) were also decreased after 12 weeks of treatment with Trehalose. Decreased serum pro-oxidant-antioxidant balance and increased GPX activity were observed at the end of the study. Decreases in mean splenic length were observed, whereas the liver volume did not change. CONCLUSION: Improvements in health-related quality of life and serum biomarkers (GAGs, liver aminotransferase levels, antioxidant status), as well as liver and spleen size, were found following 3 months of trehalose administration in patients with MPS IIIA and MPS IIIB.

Relationship between anthropometric indices and arterial stiffness: Insights from an epidemiologic study.

Background: Obesity and arteriosclerosis are both independently associated with cardiovascular disease risk. Obesity also may increase arterial stiffness. Aims: This study aimed to investigate the association between anthropometric indices and non-invasive arterial stiffness parameters, using data from a large population-based cohort of seemingly healthy women and men. Methods: A total of 5023 eligible participants were included in the study. The pulse wave velocity (PWV), central blood pressures, and bio-impedance measures were obtained at the time of enrollment. Multiple regression analysis was performed to assess the relationship between anthropometric indices with arterial stiffness parameters. Results: The mean age of participants was 45.3 ± 8.8 years, 2368 (47.1%) were males and 2655 (52.8%) were females. The prevalence of participant with underweight, normal weight, overweight, and obesity were 0.73%, 33.2%, 48.7%, and 17.2% respectively. Systolic and diastolic blood pressure, fatty liver, and hypertension were significantly higher in overweight/obesity participants. The overweight/obesity participants had significantly higher PWV than the normal-weight group (471.5 ± 42.6/496.7 ± 47.5 cm/s vs. 448.1 ± 41.4 cm/s, p < 0.001). Conclusion: The prevalence of diabetes, hypertension, fatty liver disease, chronic lung disease, and also kidney stones were significantly higher in overweight and individuals with obesity. Body mass index, body fat mass, waist-hip ratio abdominal circumference, neck circumference, visceral fat area, total body water, 50-kHz whole body phase angle are positively correlated with PWV. Augmentation index had no significant correlation with body mass index, arm, hip, and abdominal circumferences.

Meier-Gorlin syndrome with prenatal ultrasound findings and successful growth hormone therapy: Six years follow-up of a rare case.

Meire-Gorlin syndrome (MGS) is a rare autosomal recessive disorder characterized by a triad of short stature, microtia, and absent or hypoplastic patella. We report a 5-year-old male affected with the subtype MGS1, secondary to c.c2292t mutation of ORC1 gene. Our patient's features included a triangular face, micrognathia, and delayed motor development. To the edge of our knowledge, this is the first diagnosed Iranian MGS patient and sixth case in the middle east. MGS1 subtype has never shown improvement to growth hormone therapy, therefore underlying molecular defect was suggested to be responsible for patients' short stature rather than growth hormone deficiency. However, our patients' growth velocity was improved by growth hormone. We recommend more studies to specify the role of ORC1 gene in this syndrome. In addition, this case report describes the prenatal investigations and sonographic examinations of MGS1 for the first time.

Impact of Intravenous Trehalose Administration in Patients with Niemann-Pick Disease Types A and B.

BACKGROUND AND AIMS: Niemann-Pick disease (NPD) types A (NPA) and B (NPB) are caused by deficiency of the acid sphingomyelinase enzyme, which is encoded by the SMPD1 gene, resulting in progressive pathogenic accumulation of lipids in tissues. Trehalose has been suggested as an autophagy inducer with therapeutic neuroprotective effects. We performed a single-arm, open-label pilot study to assess the potential efficacy of trehalose treatment in patients with NPA and NPB patients. METHODS: Five patients with NPD type A and B were enrolled in an open-label, single-arm clinical trial. Trehalose was administrated intravenously (IV) (15 g/week) for three months. The efficacy of trehalose in the management of clinical symptoms was evaluated in patients by assessing the quality of life, serum biomarkers, and high-resolution computed tomography (HRCT) of the lungs at the baseline and end of the interventional trial (day 0 and week 12). RESULTS: The mean of TNO-AZL Preschool children Quality of Life (TAPQOL) scores increased in all patients after intervention at W12 compared to the baseline W0, although the difference was not statistically significant. The serum levels of lyso-SM-509 and lyso-SM were decreased in three and four patients out of five, respectively, compared with baseline. Elevated ALT and AST levels were decreased in all patients after 12 weeks of treatment; however, changes were not statistically significant. Pro-oxidant antioxidant balance (PAB) was also decreased and glutathione peroxidase (GPX) activity was increased in serum of patients at the end of the study. Imaging studies of spleen and lung HRCT showed improvement of symptoms in two patients. CONCLUSIONS: Positive trends in health-related quality of life (HRQoL), serum biomarkers, and organomegaly were observed after 3 months of treatment with trehalose in patients with NPA and NPB. Although not statistically significant, due to the small number of patients enrolled, these results are encouraging and should be further explored.

The Effect of Curcumin Supplementation on Pulse Wave Velocity in Patients with Metabolic Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial.

Cardiovascular disease is a leading cause of death in many societies. Arterial stiffness is an initial sign of structural and functional changes in the arterial wall. Pulse wave velocity (PWV) is the gold standard for non-invasive evaluation of aortic stiffness and a modifiable cardiovascular risk factor. Curcumin is a major component of turmeric with known anti-inflammatory and anti-oxidative effects. Since arterial stiffness is affected by inflammation and oxidative stress, it may be improved by curcumin supplementation. The purpose of this clinical trial was to investigate the potential effects of curcumin on improving arterial stiffness in patients with metabolic syndrome. This placebo-controlled, double-blind, randomized clinical trial was conducted among metabolic syndrome patients. Sixty-six eligible individuals were randomly assigned to active intervention or control groups. The active intervention group received curcumin supplement at a dose of 500 mg daily for 12 weeks, whereas the control group received placebo capsule. Physical activity, daily dietary energy intake, anthropometric body composition, and biochemical hemodynamic and arterial stiffness parameters were evaluated at baseline and at the end of the study. Body weight decreased significantly in the curcumin group compared to placebo. Also, curcumin intervention improved PWV, which remained significant after adjustment for potential confounding factors (p = 0.011). The current clinical trial demonstrated that daily intake of 500 mg of curcumin for 12 weeks can lead to the improvement of arterial stiffness and weight management among subjects with metabolic syndrome.

Role of miRNA gene variants in the susceptibility and pharmacogenetics of colorectal cancer.

Colorectal cancer (CRC) is one of the most significant challenges in the field of cancer pathology. miRNAs are among the genetic factors associated with the disease. Although many studies have reviewed the expression patterns of various miRNAs in CRC, few studies have focused on different variants of miRNA. In the present review, miRNA variants have been categorized into three subgroups, including miRNA variants that predict susceptibility to CRC, miRNA variants that predict the clinical parameters of CRC and finally, miRNA variants that predict the pharmacological aspects of CRC. Moreover, a comprehensive review of potentially functional miRNA-associated SNPs as well as their importance as candidate cancer biomarkers are discussed.

Wolcott-Rallison syndrome in Iran: a common cause of neonatal diabetes.

Background Wolcott-Rallison syndrome is a rare autosomal recessive disorder characterized by neonatal/early-onset non-autoimmune insulin-dependent diabetes, multiple epiphyseal dysphasia and growth retardation. It is caused by mutations in the gene encoding eukaryotic translation initiation factor 2α kinase 3 (EIF2AK3). We aimed to study the clinical characteristics and frequency of the disease in the Iranian population. Methods We recruited 42 patients who referred to the endocrine and metabolism clinic at Mashhad Imam Reza Hospital with neonatal diabetes. Molecular screening of KCNJ11, INS, ABCC8 and EIF2AK3 was performed at the Exeter Molecular Genetics Laboratory, UK. We calculated the frequency of the disease in 124 patients referred from Iran to the Exeter Molecular Genetics Laboratory for genetic screening and compared it to other countries worldwide. Results We identified seven patients as having Wolcott-Rallison syndrome. Genetic testing confirmed the clinical diagnosis and indicated five novel mutations. Only two patients developed clinical features of the syndrome by 6 months of age. Of all 124 cases of Iranian neonatal diabetes referred to the Exeter Molecular Genetics Laboratory for genetic screening, 28 patients (22.58%) had a recessive mutation in EIF2AK3. Conclusions The results of this study raises awareness of the condition and provides further accurate data on the genetic and clinical presentation of Wolcott-Rallison syndrome in the Iranian population. Our study highlights the importance of genetic testing in patients from consanguineous families with diabetes diagnosed within the first 6 months of life.