ProSavin is an equine infectious anemia virus vector-based gene therapy for Parkinson's disease for which inducible HEK293T-based producer cell lines (PCLs) have been developed. These cell lines demonstrate stringent tetracycline-regulated expression of the packaging components and yield titers comparable to the established transient production system. A prerequisite for the use of PCL-derived lentiviral vectors (LVs) in clinical applications is the thorough characterization of both the LV and respective PCL with regard to identity and genetic stability. We describe the detailed characterization of two ProSavin PCLs (PS5.8 and PS46.2) and resultant ProSavin vector. The two cell lines demonstrate stable production of vector over a time period sufficient to allow generation of master and working cell banks, and subsequent large-scale vector production. ProSavin generated from the PCLs performs comparably in vivo to that produced by the standard transient transfection process with respect to transduction efficiency and immunogenicity. The development of ProSavin PCLs, and the detailed characterization described here, will aid the advancement of ProSavin for clinical application.

Dementia and cancer are becoming increasingly prevalent in Western countries. In the last two decades, research focused on Alzheimer’s disease (AD) and cancer, in particular, breast cancer (BC) and prostate cancer (PC), has been substantially funded both in Europe and worldwide. While scientific research outcomes have contributed to increase our understanding of the disease etiopathology, still the prevalence of these chronic degenerative conditions remains very high across the globe. By definition, no model is perfect. In particular, animal models of AD, BC, and PC have been and still are traditionally used in basic/fundamental, translational, and preclinical research to study human disease mechanisms, identify new therapeutic targets, and develop new drugs. However, animals do not adequately model some essential features of human disease; therefore, they are often unable to pave the way to the development of drugs effective in human patients. The rise of new technological tools and models in life science, and the increasing need for multidisciplinary approaches have encouraged many interdisciplinary research initiatives. With considerable funds being invested in biomedical research, it is becoming pivotal to define and apply indicators to monitor the contribution to innovation and impact of funded research. Here, we discuss some of the issues underlying translational failure in AD, BC, and PC research, and describe how indicators could be applied to retrospectively measure outputs and impact of funded biomedical research.

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Publication of scientific findings is a fundamental part of the research process that pushes innovation and generates policies and interventions that benefit society, but it is not without biases. Publication bias is generally recognized as journal's preference for publishing studies based on the direction and magnitude of results. However, early evidence of a new type of bias related to publication has emerged in which editorial policy and/or peer reviewers or editors request that animal data be provided to validate studies produced using nonanimal human biology-based approaches. We describe herein "animal-reliance bias" in publishing: a reliance on or preference for animal-based methods where they may not be necessary or where nonanimal-based methods may be suitable, which affects the likelihood of a manuscript being accepted for publication. To gather evidence of the occurrence of this emerging type of publication bias, we set out to collect the experiences and perceptions of scientists and reviewers related to animal- and nonanimal-based experiments during peer review. To this end, we created a survey with 33 questions that was completed by 90 respondents working in several areas in the biological and biomedical fields. Twenty-one survey respondents indicated that they have carried out animal-based experiments for the sole purpose of anticipating reviewer requests. Thirty-one survey respondents indicated that they have been asked by peer reviewers to add animal experimental data to their nonanimal study; 14 of these felt that it was sometimes justified, and 11 did not think the request was justified. The data presented strongly support the occurrence of animal-reliance bias and indicates that status quo and conservatism biases may explain such attitudes by peer reviewers and editors. To our knowledge, this is the first study to recognize the existence of animal-reliance bias in publishing and provides the basis for developing strategies to prevent this practice from happening.

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