Effect of Gene Therapy on Visual Function in Leber's Congenital Amaurosis

Early-onset, severe retinal dystrophy caused by mutations in the gene encoding retinal pigment epithelium–specific 65-kD protein (RPE65) is associated with poor vision at birth and complete loss of vision in early adulthood. We administered to three young adult patients subretinal injections of recombinant adeno-associated virus vector 2/2 expressing RPE65 complementary DNA (cDNA) under the control of a human RPE65 promoter. There were no serious adverse events. There was no clinically significant change in visual acuity or in peripheral visual fields on Goldmann perimetry in any of the three patients. We detected no change in retinal responses on electroretinography. One patient had significant improvement in visual function on microperimetry and on dark-adapted perimetry. This patient also showed improvement in a subjective test of visual mobility. These findings provide support for further clinical studies of this experimental approach in other patients with mutant RPE65. (ClinicalTrials.gov number, NCT00643747.)Supported by grants from the U.K. Department of Health, the British Retinitis Pigmentosa Society, and the Special Trustees of Moorfields Eye Hospital, and by the Sir Jules Thorn Charitable Trust, the Wellcome Trust, the European Union (EVI-Genoret and Clinigene programs), the Medical Research Council, Foundation Fighting Blindness, Fight for Sight, the Ulverscroft Foundation, Fighting Blindness (Ireland), Moorfields Eye Hospital, and Institute of Ophthalmology Biomedical Research Centre for Ophthalmology, University College London

A História da Alimentação: balizas historiográficas

Os M. pretenderam traçar um quadro da História da Alimentação, não como um novo ramo epistemológico da disciplina, mas como um campo em desenvolvimento de práticas e atividades especializadas, incluindo pesquisa, formação, publicações, associações, encontros acadêmicos, etc. Um breve relato das condições em que tal campo se assentou faz-se preceder de um panorama dos estudos de alimentação e temas correia tos, em geral, segundo cinco abardagens Ia biológica, a econômica, a social, a cultural e a filosófica!, assim como da identificação das contribuições mais relevantes da Antropologia, Arqueologia, Sociologia e Geografia. A fim de comentar a multiforme e volumosa bibliografia histórica, foi ela organizada segundo critérios morfológicos. A seguir, alguns tópicos importantes mereceram tratamento à parte: a fome, o alimento e o domínio religioso, as descobertas européias e a difusão mundial de alimentos, gosto e gastronomia. O artigo se encerra com um rápido balanço crítico da historiografia brasileira sobre o tema

Adolescent diet and physical activity in the context of economic, social and nutrition transition in rural Maharashtra, India: a qualitative study

Objective:To explore the perceptions of adolescents and their caregivers on drivers of diet and physical activity in rural India in the context of ongoing economic, social and nutrition transition.Design:A qualitative study comprising eight focus group discussions (FGD) on factors affecting eating and physical activity patterns, perceptions of health and decision-making on food preparation.Setting:Villages approximately 40–60 km from the city of Pune in the state of Maharashtra, India.Participants:Two FGD with adolescents aged 10–12 years (n 20), two with 15- to 17- year-olds (n 18) and four with their mothers (n 38).Results:Dietary behaviour and physical activity of adolescents were perceived to be influenced by individual and interpersonal factors including adolescent autonomy, parental influence and negotiations between adolescents and caregivers. The home food environment, street food availability, household food security and exposure to television and digital media were described as influencing behaviour. The lack of facilities and infrastructure was regarded as barriers to physical activity as were insufficient resources for public transport, safe routes for walking and need for cycles, particularly for girls. It was suggested that schools take a lead role in providing healthy foods and that governments invest in facilities for physical activity.Conclusions:In this transitioning environment, that is representative of many parts of India and other Lower Middle Income Countries (LMIC), people perceive a need for interventions to improve adolescent diet and physical activity. Caregivers clearly felt that they had a stake in adolescent health, and so we would recommend the involvement of both adolescents and caregivers in intervention design.<br/

Food choice in transition: adolescent autonomy, agency, and the food environment

Dietary intake during adolescence sets the foundation for a healthy life, but adolescents are diverse in their dietary patterns and in factors that influence food choice. More evidence to understand the key diet-related issues and the meaning and context of food choices for adolescents is needed to increase the potential for impactful actions. The aim of this second Series paper is to elevate the importance given to adolescent dietary intake and food choice, bringing a developmental perspective to inform policy and programmatic actions to improve diets. We describe patterns of dietary intake, then draw on existing literature to map how food choice can be influenced by unique features of adolescent development. Pooled qualitative data is then combined with evidence from the literature to explore ways in which adolescent development can interact with sociocultural context and the food environment to influence food choice. Irrespective of context, adolescents have a lot to say about why they eat what they eat, and insights into factors that might motivate them to change. Adolescents must be active partners in shaping local and global actions that support healthy eating patterns. Efforts to improve food environments and ultimately adolescent food choice should harness widely shared adolescent values beyond nutrition or health

Long-Term Effect of Gene Therapy on Leber’s Congenital Amaurosis

BackgroundMutations in RPE65 cause Leber's congenital amaurosis, a progressive retinal degenerative disease that severely impairs sight in children. Gene therapy can result in modest improvements in night vision, but knowledge of its efficacy in humans is limited.MethodsWe performed a phase 1-2 open-label trial involving 12 participants to evaluate the safety and efficacy of gene therapy with a recombinant adeno-associated virus 2/2 (rAAV2/2) vector carrying the RPE65 complementary DNA, and measured visual function over the course of 3 years. Four participants were administered a lower dose of the vector, and 8 were administered a higher dose. In a parallel study in dogs, we investigated the relationship among vector dose, visual function, and electroretinography (ERG) findings.ResultsImprovements in retinal sensitivity were evident, to varying extents, in six participants for up to 3 years, peaking at 6 to 12 months after treatment and then declining. No associated improvement in retinal function was detected by means of ERG. Three participants had intraocular inflammation, and two had clinically significant deterioration of visual acuity. The reduction in central retinal thickness varied among participants. In dogs, RPE65 gene therapy with the same vector at lower doses improved vision-guided behavior, but only higher doses resulted in improvements in retinal function that were detectable with the use of ERG.ConclusionsGene therapy with rAAV2/2 RPE65 vector improved retinal sensitivity, albeit modestly and temporarily. Comparison with the results obtained in the dog model indicates that there is a species difference in the amount of RPE65 required to drive the visual cycle and that the demand for RPE65 in affected persons was not met to the extent required for a durable, robust effect. (Funded by the National Institute for Health Research and others; ClinicalTrials.gov number, NCT00643747.)