Effect of EPI-743 on the clinical course of the mitochondrial disease Leber hereditary optic neuropathy.

OBJECTIVE: To evaluate the safety and efficacy of a new therapeutic agent, EPI-743, in Leber hereditary optic neuropathy (LHON) using standard clinical, anatomic, and functional visual outcome measures. DESIGN: Open-label clinical trial. SETTING: University medical center. Patients Five patients with genetically confirmed LHON with acute loss of vision were consecutively enrolled and treated with the experimental therapeutic agent EPI-743 within 90 days of conversion. Intervention During the course of the study, 5 consecutive patients received EPI-743, by mouth, 3 times daily (100-400 mg per dose). MAIN OUTCOME MEASURES: Treatment effect was assessed by serial measurements of anatomic and functional visual indices over 6 to 18 months, including Snellen visual acuity, retinal nerve fiber layer thickness measured by optical coherence tomography, Humphrey visual fields (mean decibels and area with 1-log unit depression), and color vision. Treatment effect in this clinical proof of principle study was assessed by comparison of the prospective open-label treatment group with historical controls. RESULTS: Of 5 subjects treated with EPI-743, 4 demonstrated arrest of disease progression and reversal of visual loss. Two patients exhibited a total recovery of visual acuity. No drug-related adverse events were recorded. CONCLUSIONS: In a small open-label trial, EPI-743 arrested disease progression and reversed vision loss in all but 1 of the 5 consecutively treated patients with LHON. Given the known natural history of acute and rapid progression of LHON resulting in chronic and persistent bilateral blindness, these data suggest that the previously described irreversible priming to retinal ganglion cell loss may be reversed

The making of modern scientific personae: the scientist as a moral person? Emil Du Bois-Reymond and his friends

This article examines the notion of the \u27scientist as a moral person\u27 in the light of the early stages of the commodification of science and the transformation of research into a big enterprise, operating on the principle of the division of labour. These processes were set in train at the end of the 19th century. The article focuses on the concomitant changes in the public persona and the habitus of scientific entrepreneurs. I begin by showing the significance of the professional networks that were built up and maintained to further a group\u27s research ideas and the careers of its members, thus demonstrating one condition on which depended their practice of science and their ability to earn a living. This leads to a characterization of the changing styles of work, thought and life, and to a consideration of public perceptions and of the ways in which a new self-image of scholarship and science was fashioned. A critical discussion of the public role of these mandarin scientists follows in order to highlight the strains created by the commodification of science at a time of international tensions and conflicts, when shared beliefs in scholarly cosmopolitanism were subverted by appeals to science and scholarship to work in the service of one\u27s own nation as its \u27courtiers\u27. Various considerations of peculiar analogies between national styles of research and the style of social organization are then noted. In the final section, the article queries the long-term impact of these developments on the ideal of the scientist as a \u27moral person\u27. Taking a cue from Max Weber and pursuing reflections by Zygmunt Bauman on \u27science moralized\u27, I argue that the emergence of a type of \u27specialists without spirit\u27 was an unintended but fatal consequence of the changes in research practices promoted by scientific entrepreneurs such as Du Bois-Reymond. I conclude that the temptation to sever the ties to a general ethos of civil virtues lay in the rationalization, specialization and potential de-humanization of the objectifying scientific outlook once advocated for its efficiency.<br /