Role of Dynein Axonemal Heavy Chain 6 Gene Expression as a Possible Biomarker for Huntington's Disease: a Translational Study.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterized by motor dysfunction, cognitive deficits, and psychiatric symptoms. The primary genetic cause is an expansion of cytosine adenine guanine (CAG) nucleotides of the huntingtin gene, which codes an important protein involved with neuronal signaling. The severity of HD correlates with the number of CAG repeats and individuals with longer expansions have an earlier onset and more severe symptoms. A microarray study conducted by our research group showed alteration in DNAH6 gene (encoding dynein axonemal heavy chain 6). DNAH6 belongs to dynein family, whose members are constituents of the microtubule-associated motor proteins and is downregulated in the striatum of a HD mouse model (knockin HdhQ111/Q111). In this manner, our goal was to confirm these downregulations in the mouse model and verify if the same alteration in the axonemal DNAH6 gene expression is observed in blood samples of HD patients. Blood samples were collected from 17 patients with clinical diagnosis of HD and 12 healthy individuals and RNA extracted for qPCR analysis. Microarray data were confirmed by qPCR in knockin HdhQ111/Q111, and DNAH6 was severely decreased in those mice, as compared to control mice (HdhQ20/Q20). Notably, decreased expression of DNAH6 gene was also observed in HD patients when compared to control group and negatively correlates with the CAG expansion. Although further studies are necessary to underlie the molecular mechanisms of dynein-htt interaction, this data highlights DNAH6 as a potential new blood marker for HD.

A novel multidisciplinary intervention for long-term weight loss and glycaemic control in obese patients with diabetes.

INTRODUCTION: Obesity and diabetes are difficult to treat in public clinics. We sought to determine the effectiveness of the Metabolic Rehabilitation Program (MRP) in achieving long-term weight loss and improving glycaemic control versus "best practice" diabetes clinic (DC) in obese patients using a retrospective cohort study. METHODS: Patients with diabetes and BMI > 30 kg/m(2) who attended the MRP, which consisted of supervised exercise and intense allied health integration, or the DC were selected. Primary outcomes were improvements in weight and glycaemia with secondary outcomes of improvements in blood pressure and lipid profile at 12 and 30 months. RESULTS: Baseline characteristics of both cohorts (40 MRP and 40 DC patients) were similar at baseline other than age (63 in MRP versus 68 years in DC, P = 0.002). At 12 months, MRP patients lost 7.65 ± 1.74 kg versus 1.76 ± 2.60 kg in the DC group (P < 0.0001) and 9.70 ± 2.13 kg versus 0.98 ± 2.65 kg at 30 months (P < 0.0001). Similarly, MRP patients had significant absolute reductions in %HbA1c at 30 months versus the DC group (-0.86 ± 0.31% versus 0.12% ± 0.33%, P < 0.038), with nonsignificant improvements in lipids and blood pressure in MRP patients. CONCLUSION: Further research is needed to establish the MRP as an effective strategy for achieving sustained weight loss and improving glycaemic control in obese patients with type 2 diabetes.