Protection of retinal ganglion cells in glaucoma: Current status and future.

Glaucoma is a neuropathic disease that causes optic nerve damage, loss of retinal ganglion cells (RGCs), and visual field defects. Most glaucoma patients have no early signs or symptoms. Conventional pharmacological glaucoma medications and surgeries that focus on lowering intraocular pressure are not sufficient; RGCs continue to die, and the patient's vision continues to decline. Recent evidence has demonstrated that neuroprotective approaches could be a promising strategy for protecting against glaucoma. In the case of glaucoma, neuroprotection aims to prevent or slow down disease progression by mitigating RGCs death and optic nerve degeneration. Notably, new pharmacologic medications such as antiglaucomatous agents, antibiotics, dietary supplementation, novel neuroprotective molecules, neurotrophic factors, translational methods such as gene therapy and cell therapy, and electrical stimulation-based physiotherapy are emerging to attenuate the death of RGCs, or to make RGCs resilient to attacks. Understanding the roles of these interventions in RGC protection may offer benefits over traditional pharmacological medications and surgeries. In this review, we summarize the recent neuroprotective strategy for glaucoma, both in clinical trials and in laboratory research.

The path from scientific discovery to cures for epilepsy.

The epilepsies are a complex group of disorders that can be caused by a myriad of genetic and acquired factors. As such, identifying interventions that will prevent development of epilepsy, as well as cure the disorder once established, will require a multifaceted approach. Here we discuss the progress in scientific discovery propelling us towards this goal, including identification of genetic risk factors and big data approaches that integrate clinical and molecular 'omics' datasets to identify common pathophysiological signatures and biomarkers. We discuss the many animal and cellular models of epilepsy, what they have taught us about pathophysiology, and the cutting edge cellular, optogenetic, chemogenetic and anti-seizure drug screening approaches that are being used to find new cures in these models. Finally, we reflect on the work that still needs to be done towards identify at-risk individuals early, targeting and stopping epileptogenesis, and optimizing promising treatment approaches. Ultimately, developing and implementing cures for epilepsy will require a coordinated and immense effort from clinicians and basic scientists, as well as industry, and should always be guided by the needs of individuals affected by epilepsy and their families. This article is part of the special issue entitled 'New Epilepsy Therapies for the 21st Century - From Antiseizure Drugs to Prevention, Modification and Cure of Epilepsy'.

Intravascular cell therapy in stroke: predicting the future trends.

This short review examines the trends that have taken place during the last two decades in selecting delivery route and cell product in confirmatory preclinical stroke research. If there had been a major change, this might indicate a strategy with a high potential to enter early-phase clinical studies. The retrospective data show that intravenous cell delivery of mesenchymal stem cells remains the most popular approach in experimental research, clearly dominating early phase clinical studies. The advantages and risks of current practices are discussed in the hope that these will improve translational success and accelerate clinical development of safe and efficient cell products.

Where biomedicalisation and magic meet: Therapeutic innovations of elite sports injury in British professional football and cycling.

Injury is a conspicuous feature of the practice and public spectacle of contemporary elite sports. The paper argues that the 'biomedicalisation' thesis (medico-industrial nexus, techno-scientific drivers, medical optimisation, biologisation, the rise of evidence and health surveillance) goes some way to capturing the use in elite sports injury of some highly specialised mainstream therapies and some highly maverick biological therapies, which are described. Nevertheless, these main strands of biomedicalisation do not capture the full range of these phenomena in the contexts of sports medicine and athletes' practices in accessing innovative, controversial therapies. Drawing on multi-method qualitative research on top-level professional football and cycling in the UK, 2014-2016, we argue that concepts of 'magic' and faith-based healing, mediated by notions of networking behaviour and referral systems, furnish a fuller explanation. We touch on the concept of 'medical pluralism', concluding that this should be revised in order to take account of belief-based access to innovative bio-therapies amongst elite sportspeople and organisations.

Riesgo y seguridad de la terapia avanzada / Risks and safety of advanced therapy

Los riesgos inherentes a la terapia avanzada identificar los riesgos potenciales y mitigarlos mediante controles adecuados. Gracias en parte a la información obtenida en todas las etapas desarrollo. Las diferencias entre terapia celular, terapia génica e ingeniería de tejidos nos muestran los riesgos específicos para cada tipo de terapia. Pues la terapia génica podría generar efectos permanentes con una sola dosis. El seguimiento de la eficacia y las reacciones adversas son aspectos cruciales de la reglamentación de los medicamentos de terapia avanzada

The risks inherent in the advanced therapy identify potential risks and mitigate them through appropriate controls. Thanks in part to the information obtained in all development stages. The differences between cell therapy, gene therapy and tissue engineering show us the risks specific to each type of therapy. Because gene therapy could generate lasting effects with a single dose. Follow-up of efficacy and adverse reactions are crucial aspects of advanced therapy medicines regulation

Regenerative medicine: transforming the drug discovery and development paradigm.

Despite the explosion of knowledge in basic biological processes controlling tissue regeneration and the growing interest in repairing/replacing diseased tissues and organs through various approaches (e.g., small and large molecule therapeutics, stem cell injection, tissue engineering), the pharmaceutical industry (pharma) has been reluctant to fully adopt these technologies into the traditional drug discovery and research and development (R&D) process. In this article, I discuss knowledge-base gaps and other possible factors that may delay full incorporation of these innovations in pharma R&D. I hope that this discussion will illuminate key issues that currently limit synergistic relationships between pharma and academic institutions and may even stimulate initiation of such collaborative research.

Future perspective of induced pluripotent stem cells for diagnosis, drug screening and treatment of human diseases.

Recent advances in stem cell biology have transformed the understanding of cell physiology and developmental biology such that it can now play a more prominent role in the clinical application of stem cell and regenerative medicine. Success in the generation of human induced pluripotent stem cells (iPS) as well as related emerging technology on the iPS platform provide great promise in the development of regenerative medicine. Human iPS cells show almost identical properties to human embryonic stem cells (ESC) in pluripotency, but avoid many of their limitations of use. In addition, investigations into reprogramming of somatic cells to pluripotent stem cells facilitate a deeper understanding of human stem cell biology. The iPS cell technology has offered a unique platform for studying the pathogenesis of human disease, pharmacological and toxicological testing, and cell-based therapy. Nevertheless, significant challenges remain to be overcome before the promise of human iPS cell technology can be realised.

Potential applications of human embryonic stem cells.

Advances in reproductive technologies provided opportunity for scientists to be able to grow human embryos in vitro for more than two decades. Skills and knowledge derived from in vitro fertilization and in vitro culture of mammalian embryos opened the chance for scientists to develop the strategies to derive embryonic stem cell lines from mammalian and human embryos. This achievement has initiated a new era in the fields of biotechnology, pharmacology, basic scientific research, and cell-based medicine. To date, scientists have made some progress in optimizing regimens in deriving ES cell lines from human embryos but much more research and development are still required especially in the aspect of directing stem cells into the specific cells of potential clinical use. Collaboration among clinicians and scientists from diverse fields, together with the public awareness of how useful this technology could be to modern medicine, will result in the accumulation of knowledge in this field and, in the near future, a progress in cell-based therapy.

Huntington's disease: new frontiers for molecular and cell therapy.

Huntington's disease (HD) is an incurable, adult-onset, dominantly inherited neurodegenerative disease, caused by a CAG expansion in the 5' coding region of the gene HD [encoding huntingtin (htt), which is ubiquitously expressed in all tissues]. The disease progresses inexorably with devastating clinical effects on motor, cognitive and psychological functions; death occurring approximately 18 years from the time of onset. These clinical symptoms primarily relate to the progressive death of medium-spiny GABA-ergic neurons of the striatum and in the deep layers of the cortex; during the later stages of the disease, the degeneration extends to a variety of brain regions, including the hypothalamus and hippocampus. The mechanism by which mutant htt leads to neuronal cell death and the question of why striatal neurons are targeted both remain to be further investigated. Certainly htt is required for cell survival and impairment of wild-type htt function can be involved in neurodegeneration, but considerable evidence also shows that trinucleotide repeat expansion into glutamine (polyQ domain) endows the protein with a newly acquired toxic activity. The increasing availability of HD animal models have allowed not only to investigate the function of htt, but also to screen and test potential therapeutic drugs in the promising area of neurotherapeutics. So, thorough analysis of these molecular and biochemical events, assessing the validity of candidate mechanisms, provides a means to identify effective therapeutic strategies for cellular repair. Here, the rationale and efficacy of different therapies are compared and alternative therapies are reviewed including intrastriatal transplantation of human fetal striatal tissue to support the cell replacement strategy in HD. Since functional restoration through neuronal replacement probably could be combined with neuroprotective strategies for optimum clinical benefit, in vivo and ex vivo gene therapy for delivery of neuroprotective growth factor molecules are also considered.