Reviews

P. Race, 500 Tips on Group Learning, London: Kogan Page, 2000. ISBN: 0–7494–2884–8. Softback, vii + 135 pages, £15.99

From Value Protection to Value Creation: Rethinking Corporate Governance Standards for Firm Innovation

A company’s pro-innovation needs are often met by the exploitation of its resources, widely defined. The resource-based theory of the firm provides immense empirical insights into how a firm’s corporate governance factors can contribute to promoting innovation. However, these implications may conflict with the prevailing standards of corporate governance imposed on many securities markets for listed companies, which have developed based on theoretical models supporting a shareholder-centered and agency-based theory of the firm. Although prevailing corporate governance standards can to an extent support firm innovation, tensions are created in some circumstances where companies pit their corporate governance compliance against resource-based needs that promote innovation. In the present context of steady internationalization and convergence in corporate governance standards in global securities markets towards a shareholder-centered agency-based model, we argue that there is a need to provide some room for accommodating the resource-based needs for companies in relation to promoting innovation. We explore a number of options and suggest that the most practicable option would be the development of recognized exceptions that deviate from prevailing corporate governance standards. We further suggest as to how an exceptions-based regime can be implemented in the U.K. and U.S., comparing the rules-based regime in the U.S. with the principles-based regime in the U.K

Implantation of the clinical-grade human neural stem cell line, CTX0E03, rescues the behavioral and pathological deficits in the quinolinic acid-lesioned rodent model of Huntington’s disease

Huntington’s disease (HD) is a devastating, autosomal-dominant neurodegenerative disease, for which there are currently no disease-modifying therapies. Clinical trials to replace the damaged striatal medium spiny neurons (MSN) have been attempted in the past two decades but have met with only limited success. In this study, we investigated whether a clonal, conditionally immortalized neural stem cell line (CTX0E03), which has already shown safety and signals of efficacy in chronic ischemic stroke patients, could rescue deficits seen in an animal model of HD. After CTX0E03 transplantation into the quinolinic acid (QA)-lesioned rat model of HD, behavioral changes were measured using the rotarod, stepping and staircase tests. In vivo differentiation and neuronal connections of the transplanted CTX0E03 cells was evaluated with immunohistochemical staining and retrograde tracing with Fluoro-Gold. We found that transplantation of CTX0E03 gave rise to a significant behavioral improvement compared with the sham- or fibroblast-transplanted group. Transplanted CTX0E03 formed medium spiny neurons (MSNs) (DARPP-32) and GABAergic neurons (GABA, GAD65/67) with BDNF expression in the striatum, while cortically transplanted cells formed Tbr1-positive neurons. Using a retrograde-label we also found stable engraftment and connection of the transplanted cells with host brain tissues. CTX0E03 transplantation also reduced glial scar formation and inflammation, as well as increasing endogenous neurogenesis and angiogenesis. Overall, our results demonstrate that CTX0E03, a clinical-grade neural stem cell line, is effective for pre-clinical test in HD, and, therefore, will be useful for clinical development in the treatment of HD patients.This research was supported by the National Research Foundation of Korea (NRF14 2017M3A9B4061407), Republic of Korea and by the internal funding of ReNeuron, United Kingdom and iPS Bio, Inc., Republic of Korea

A Professional Standard for Informed Consent for Stem Cell Therapies

In November 2018, the US Food & Drug Administration (FDA) issued a press release that stated: “The potential health benefits of regenerative medicine have spurred major progress in stem-cell biology over the past several decades. But we continue to see bad actors exploit the scientific promise of this field to mislead vulnerable patients into believing they’re being given safe, effective treatments; when instead these stem cell producers are leveraging the field’s hype to push unapproved, unproven, illegal, and potentially unsafe products."Non

The Labor Market Determinants of Corporate Governance Reform

A theoretical framework is presented that connects change in the organization of labor with change in corporate governance and financial system development. Building on work by Rueda (2005, 2006, 2007), the paper considers labor change in terms of reduced insiderness and examines how this might impact on the orientation of corporate governance vis-à-vis blockholders and minority shareholders. The proposed relationship is investigated utilizing a panel of data for the advanced industrialized democracies

Reviews

Anne Brockbank, Ian McGill and Nic Beech, Reflective Learning in Practice, Aldershot: Gower Publishing, ISBN: 0 566 08377 9. £49.50

Rating Apathy in Huntington’s Disease: Patients and Companions Agree.

BACKGROUND: Apathy is a common feature of Huntington’s disease (HD), even from early disease. However, patients are believed to lack insight into their own apathy and therefore clinicians and/or companions are relied upon to estimate the extent of a patient’s apathy. In addition, the evolution of apathy over time in HD has not been unequivocally established. OBJECTIVEs: The purpose of this study was to determine whether HD patient’s self-rated apathy scores were consistent with the scores given by companions who were also asked to rate the patients apathy. Furthermore, the clinical correlates of apathy and its stability over time were examined for both self-rated and companion-rated scores. METHODs: Apathy was measured in a large cross-sectional population of HD patients ranging from early to late stage disease (n = 106) using the Apathy Evaluation Scale; a subgroup of whom were followed longitudinally (n = 62) on average 18.7 (1.2 SD) months later. Comparisons were made between self-rated and companion-rated apathy and the relationship between apathy and motor, cognitive and functional performance was explored. RESULTS: Analysis of the cross-sectional data revealed that self-rated and companion-rated apathy were highly correlated, establishing the validity of using self-rated instead of, or in combination with, companion-rated assessments of apathy in future studies. Both self-rated and companion-rated scores had a relationship with motor and functional impairment, but had a complex relationship with cognition. The results of the longitudinal comparison revealed that apathy did not change over time in this cohort.CONCLUSIONs: Apathy can be equally well assessed by either patients or companions and does not change significantly over an18 month period. These findings have implications in the design of studies looking at treating this important aspect of HD.The work included in this manuscript has been partially funded by financial support from the NIHR Cambridge Biomedical Research Centre and the Cambridge University NHS Foundation Trust.This is the accepted manuscript of a paper published in the Journal of Huntington's Disease (Mason S, Barker RA, Journal of Huntington's Disease 2015, 4, 49-59, doi:10.3233/JHD-140133). The final version is available at http://dx.doi.org/10.3233/JHD-14013

Designing stem-cell-based dopamine cell replacement trials for Parkinson's disease.

Clinical studies of Parkinson's disease (PD) using a dopamine cell replacment strategy have been tried for more than 30 years. The outcomes following transplantation of human fetal ventral mesencephalic tissue (hfVM) have been variable, with some patients coming off their anti-PD treatment for many years and others not responding and/or developing significant side effects, including graft-induced dyskinesia. This led to a re-appraisal of the best way to do such trials, which resulted in a new European-Union-funded allograft trial with fetal dopamine cells across several centers in Europe. This new trial, TRANSEURO ( NCT01898390 ), is an open-label study in which some individuals in a large observational cohort of patients with mild PD who were undergoing identical assessments were randomly selected to receive transplants of hfVM. The TRANSEURO trial is currently ongoing as researchers have completed both recruitment into a large multicenter observational study of younger onset early-stage PD and transplantation of hfVM in 11 patients. While completion of TRANSEURO is not expected until 2021, we feel that sharing the rationale for the design of TRANSEURO, along with the lessons we have learned along the way, can help inform researchers and facilitate planning of transplants of dopamine-producing cells derived from human pluripotent stem cells for future clinical trials.This study was supported by an EU FP7 grant (242003) as well as funding from the Cure Parkinson’s Trust (RG81537), John Black Charitable Trust and Multipark. The work was also supported by NIHR funding of Biomedical Research Centres at UCL and Cambridge (146281). RAB is an NIHR Senior Investigator (NF-SI-0616-10011) and a PI in the MRC/WT Stem Cell Institute (203151/Z/16/Z)

The hunt for better treatments for Huntington's disease.

Huntington’s Disease (HD) is an autosomal dominant condition that typically presents in midlife with a combination of motor, cognitive and psychiatric problems along with sleep and metabolic abnormalities. It runs a clinical course over 15-20 years leading to death as patients become demented and bed bound. There are currently no proven disease modifying therapies for HD. While the recent work with anti-sense therapies (ASO) against huntingtin has generated much excitement they are yet to demonstrate a measurable change in disease progression. Furthermore, given they promise to “modify” and not “cure” HD patients we will still require adjunct symptomatic treatments, potentially for longer periods of time. Symptomatic therapies for HD do exist and are widely used for treating the chorea and some of the psychiatric aspects of the condition although the extent to which they work is variable1 and many experience significant side effects with them. Therefore, there is still a need to develop better symptomatic therapies, ideally with single drugs that can help treat more than one sign and symptom of this condition

Cell replacement therapy for Parkinson's disease

AbstractParkinson's disease (PD) is a progressive neurodegenerative disorder in which the degeneration of dopaminergic neurons projecting from the substantia nigra to the striatum is a key pathological feature of the disease. Although pharmacological dopamine replacement is generally very effective in early disease, it is only a symptomatic therapy and can have significant side effects with long term use. One of the key strategies in a more restorative approach to PD therapy involves replacement of this degenerating nigro-striatal dopaminergic network with cells and several possible cell sources are being explored. While much experience and some success have been gained with fetal ventral mesencephalic (FVM) tissue transplants, the rapidly advancing stem cell field is providing attractive alternative options which circumvent many of the ethical and practical problems inherent in trials with FVM tissue. Of these embryonic stem cells and induced pluripotent stem cells seem the most promising. However further development and optimisation of the safety and efficacy of the techniques involved in generating and manipulating these, as well as other, cell sources will be essential before any further clinical trials are carried out