Intraspinal administration of human spinal cord‐derived neural progenitor cells in the G93A–SOD1 mouse model of ALS delays symptom progression,prolongs survival and increases expression of endogenous neurotrophic factors

Neural stem or progenitor cells are considered to be a novel therapeutic strategy for amyotrophic lateral sclerosis (ALS), based on their potential to generate a protective environment rather than to replace degenerating motor neurons. Following local injection to the spinal cord, neural progenitor cells may generate glial cells and release neurotrophic factors. In the present study, human spinal cord‐derived neural progenitor cells (hscNPCs) were injected into the lumbar spinal cord of G93A–SOD1 ALS transgenic mice. We evaluated the potential effect of hscNPC treatment by survival analysis and behavioural/phenotypic assessments. Immunohistological and real‐time PCR experiments were performed at a defined time point to study the underlying mechanisms. Symptom progression in hscNPC‐injected mice was significantly delayed at the late stage of disease. On average, survival was only prolonged for 5 days. Animals treated with hscNPCs performed significantly better in motor function tests between weeks 18 and 19. Increased production of GDNF and IGF‐1 mRNA was detectable in spinal cord tissue of hscNPC‐treated mice. In summary, treatment with hscNPCs led to increased endogenous production of several growth factors and increased the preservation of innervated motor neurons but had only a small effect on overall survival. Copyright © 2015 John Wiley & Sons, Ltd.     

Bisoprolol vs. carvedilol in elderly patients with heart failure: rationale and design of the CIBIS-ELD trial

Background  Chronic heart failure (CHF) is a widespread disease with severe quality of life impairment and a poor prognosis. Beta-blockers are the mainstay of CHF therapy; yet they are under-prescribed and under-dosed in clinical practice. This is particularly evident in elderly patients, which may be due to a fear of side-effects or intolerance. Beta-blockers have further not been adequately tested in patients with diastolic CHF, which is particularly common in elderly patients. Finally, comparative data on the use of different beta-blockers in patients with CHF is scarce. Aim  To compare the tolerance of bisoprolol and carvedilol in elderly patients with CHF. Methods  CIBIS-ELD is an investigator-initiated, multi-centre, 1:1 randomised, double-blind, phase III trial comparing bisoprolol and carvedilol in patients ≥65 years with systolic or diastolic CHF. Recruitment started in April 2005 and is anticipated to be completed by April 2008 with at least 800 patients enrolled. Perspective  This is the first large scale head to head beta-blockers trial in an elderly population with CHF. Besides determining which of two standard beta-blockers is best tolerated in elderly patients with systolic or diastolic CHF, we expect to gain further insight into the treatment of the particular population of patients with diastolic CHF. This trial was supported by the Competence Network of Heart Failure funded by the Federal Ministry of Education and Research (BMBF, project number 01GI0205) and is registered with number ISRCTN34827306 at .