Advancing trial design in progressive multiple sclerosis

The failure of a majority of clinical trials in progressive multiple sclerosis (MS) has highlighted the need to reconsider how these trials are designed and conducted, and many areas deserve focus. Basic scientists are reconceptualising the pathophysiology of progressive MS into three broad areas: systemic inflammation, compartmentalized inflammation and non-inflammatory neurodegeneration, with the latter two becoming predominant as the disease progresses. This framework will guide the choice of experimental therapies. Previous clinical trials have highlighted how participant selection can have a significant impact on study outcome. Phase 2 biomarkers which are biologically stable, dynamically changing over time, and easy to assess in multi-centre studies are greatly needed. Shortcomings inherent in the Expanded Disability Status Scale are prompting the development and validation of better clinical measures. The standard two-arm, fixed-duration trial paradigm has been challenged with new, innovative approaches that can test more therapies efficiently. International collaboratives such as the Progressive MS Alliance will support increased dialogue with regulators, industry and other funding agencies. Better engagement with people living with progressive MS will transform them from simply being the recipient of MS therapies to partners in the search for new treatments. Focused, targeted action will drive further development of effective therapies for progressive MS

The Structural Genomics Consortium: successful organisational technology experiment or new institutional infrastructure for health research?

In a sector characterised by patenting, direct appropriations and returns from investment, the Structural Genomics Consortium (SGC) constitutes a radically different public-private and entirely open access approach to pre-competitive research. This paper discusses the significance of findings from the first independent review of the SGC. We argue that the SGC offers a shared knowledge resource for drug discovery which is distinctive from other types of knowledge production and, as such, provides a knowledge infrastructure for the wider scientific community. We distinguish three ways in which this infrastructure functions as a model for investing in, extracting value from, and generating knowledge for the field. Our analysis suggests there is a future for open science models such as the SGC in health research and innovation, but that such models raise a set of challenges over the role of different public and private institutional actors and the way in which value is extracted

The importance of mentorship and collaboration for scientific capacity-building and capacity-sharing: perspectives of African scientists

Long-term goals for capacity-building in Africa centres around building a self-sufficient scientific community, however there is a lack of research on the interactions that are needed to make up a thriving academic community or the steps needed to realise such a goal. Through interviews with researchers supported by a capacity-building initiative, we have characterised their interactions with other scientists and the impact that these have on capacity-building. This has revealed a wide range of interactions that have not been captured by traditional bibliometric studies of collaboration and shown that a substantial amount of intra-African collaboration is taking place. This collaboration allowed the researchers to share capacity with their colleagues and this could provide an alternative to, or supplement, traditional North-South capacity-building. We have shown that this capacity-sharing can enable capacity to spill over from capacitybuilding programmes to the broader scientific community. Furthermore, researchers are deliberately hastening this capacitysharing through training or mentoring others outside of their capacity-building initiative, including those from more resource-poor groups. To understand how capacity-building initiatives can harness the power of these interactions, we investigated how interactions between researchers originated, and found that collaborations tended to be formed around pre-existing networks, with researchers collaborating with previous colleagues, or contacts formed through their mentors or consortium activities. Capacity-building organisations could capitalise on this through actions such as expanding mentorship schemes but should also ensure that researchers are not limited to pre-established networks but have exposure to a changing and growing pool of expertise. As interactions continue to move online since the appearance of COVID-19 this will present opportunities for new interaction patterns to develop. This study highlights the need to develop new metrics for collaboration that will take into account these new modes of interaction and the full range of interactions that make up a scientific community

Multiple sclerosis, a treatable disease

This article reviews our current understanding and modern treatment of multiple sclerosis (MS). MS is a disabling condition resulting in devastating social and economic impacts. As MS can affect any part of the central nervous system, the presentation is often diverse; however, there are key features that can be useful in the clinic. We comment on the diagnostic criteria and review the main subtypes of MS, including clinically isolated syndrome, relapsing remitting MS, secondary progressive MS and primary progressive MS. Although the underlying aetiology of MS is still not known, we summarise those with most evidence of association. Finally, we aim to present treatment strategies for managing the acute relapse, disease-modifying therapies and MS symptoms. This review highlights that progressive MS is an area where there is currently a paucity of available disease-modifying treatments and this will be a major focus for future development