Duchenne muscular dystrophy (DMD) is an X-linked genetic disease, caused by the absence of the dystrophin protein. Although many novel therapies are under development for DMD, there is currently no cure and affected individuals are often confined to a wheelchair by their teens and die in their twenties/thirties. DMD is a rare disease (prevalence <5/10,000). Even the largest countries do not have enough affected patients to rigorously assess novel therapies, unravel genetic complexities, and determine patient outcomes. TREAT-NMD is a worldwide network for neuromuscular diseases that provides an infrastructure to support the delivery of promising new therapies for patients. The harmonized implementation of national and ultimately global patient registries has been central to the success of TREAT-NMD. For the DMD registries within TREAT-NMD, individual countries have chosen to collect patient information in the form of standardized patient registries to increase the overall patient population on which clinical outcomes and new technologies can be assessed. The registries comprise more than 13,500 patients from 31 different countries. Here, we describe how the TREAT-NMD national patient registries for DMD were established. We look at their continued growth and assess how successful they have been at fostering collaboration between academia, patient organizations, and industry.

The EuroBioBank (EBB) network (www.eurobiobank.org) is the first operating network of biobanks in Europe to provide human DNA, cell and tissue samples as a service to the scientific community conducting research on rare diseases (RDs). The EBB was established in 2001 to facilitate access to RD biospecimens and associated data; it obtained funding from the European Commission in 2002 (5th framework programme) and started operation in 2003. The set-up phase, during the EC funding period 2003–2006, established the basis for running the network; the following consolidation phase has seen the growth of the network through the joining of new partners, better network cohesion, improved coordination of activities, and the development of a quality-control system. During this phase the network participated in the EC-funded TREAT-NMD programme and was involved in planning of the European Biobanking and Biomolecular Resources Research Infrastructure. Recently, EBB became a partner of RD-Connect, an FP7 EU programme aimed at linking RD biobanks, registries, and bioinformatics data. Within RD-Connect, EBB contributes expertise, promotes high professional standards, and best practices in RD biobanking, is implementing integration with RD patient registries and ‘omics' data, thus challenging the fragmentation of international cooperation on the field.

To investigate the contribution of inherited biochemical defects to the peripheral insulin resistance of type 2 diabetes, we studied cultured skeletal muscle from 10 insulin-resistant nondiabetic first-degree relatives of type 2 diabetic families and 6 control subjects. Insulin stimulation of glucose uptake and glycogen synthesis was maximal in myoblasts. Insulin-stimulated glucose uptake (fold-stimulation over basal uptake) was decreased in relative compared with control myoblasts at 0.001 µmol/l (0.93 ± 0.05 [mean ± SE] vs. 1.15 ± 0.06, P < 0.05) and 0.1 µmol/l (1.38 ± 0.10 vs. 1.69 ± 0.08, P = 0.025) insulin. Insulin responsiveness was markedly impaired in 5 of the relative myoblast cultures, and in 4 of these, there was an associated increase in basal glucose uptake (76.7 ± 7.0 vs. 47.4 ± 5.5 pmol · min -1 · mg -1 protein, relative vs. control; P < 0.02). Expression of insulin receptor substrate 1, phosphatidylinositol 3-kinase, protein kinase B, and glycogen synthase was normal in the relative cultures with impaired insulin responsiveness. Glycogen synthesis was also normal in the relative cultures. We conclude that the persistence of impaired insulin responsiveness in some of the relative cultures supports the role of inherited factors in the insulin resistance of type 2 diabetes and that the association with increased basal glucose uptake suggests that the 2 abnormalities may be linked.

Aim/hypothesis Pancreatic beta cell function has been shown to decline with age in man. Depletion of mitochondrial DNA (mtDNA) copy number is associated with impaired insulin secretion in pancreatic beta cell lines, and decreased mtDNA copy number has been observed with age in skeletal muscle in man. We investigated whether mtDNA copy number decreases with age in human pancreatic beta cells, which might in turn contribute to the age-related decline in insulin secretory capacity. Methods We quantified mtDNA copy number in isolated human islet preparations from 15 pancreas donors aged between 17 and 75 years. Islets (n=20) were individually hand-picked and pooled from each donor isolate for the quantification of mtDNA copy number and deleted mtDNA (%), which were determined using real-time PCR methods. Results There was a significant negative correlation between mtDNA copy number and islet donor age (r=-0.53, p=0.044). mtDNA copy number was significantly decreased in islet preparations from donors aged ≥50 years (n=8) compared with those aged <50 years (n=7) (median [interquartile range]: 418 [236-503] vs 596 mtDNA copy number/diploid genome; p=0.032). None of the islet preparations harboured high levels of deleted mtDNA affecting the major arc. Conclusion/interpretation Given the correlation between mtDNA content and respiratory chain activity, the agerelated decrease in mtDNA copy number that we observed in human pancreatic islet preparations may contribute to the age-dependent decline in pancreatic beta cell insulin secretory capacity.