Stroke is the second leading cause of death worldwide and a leading cause of disability. Most strokes are caused by occlusion of a major cerebral artery, and substantial advances have been made in elucidating how ischemia damages the brain. In particular, increasing evidence points to a double-edged role of the immune system in stroke pathophysiology. In the acute phase, innate immune cells invade brain and meninges and contribute to ischemic damage, but may also be protective. At the same time, danger signals released into the circulation by damaged brain cells lead to activation of systemic immunity, followed by profound immunodepression that promotes life-threatening infections. In the chronic phase, antigen presentation initiates an adaptive immune response targeted to the brain, which may underlie neuropsychiatric sequelae, a considerable cause of poststroke morbidity. Here, we briefly review these pathogenic processes and assess the potential therapeutic value of targeting immunity in human stroke.

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Immune responses to stroke: mechanisms, modulation, and therapeutic potential.

The mission of the social sciences is to understand and ameliorate society’s greatest challenges. The data held by private companies, collected for different purposes, hold vast potential to further this mission. Yet, because of consumer privacy, trade secrets, proprietary content, and political sensitivities, these datasets are often inaccessible to scholars. We propose a novel organizational model to address these problems. We also report on the first partnership under this model, to study the incendiary issues surrounding the impact of social media on elections and democracy: Facebook provides (privacy-preserving) data access; eight ideologically and substantively diverse charitable foundations provide initial funding; an organization of academics we created, Social Science One, leads the project; and the Institute for Quantitative Social Science at Harvard and the Social Science Research Council provide logistical help.

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A New Model for Industry–Academic Partnerships

Academic research plays a key role in identifying new drug targets, including understanding target biology and links between targets and disease states. To lead to new drugs, however, research must progress from purely academic exploration to the initiation of efforts to identify and test a drug candidate in clinical trials, which are typically conducted by the biopharma industry. This transition can be facilitated by a timely focus on target assessment aspects such as target-related safety issues, druggability and assayability, as well as the potential for target modulation to achieve differentiation from established therapies. Here, we present recommendations from the GOT-IT working group, which have been designed to support academic scientists and funders of translational research in identifying and prioritizing target assessment activities and in defining a critical path to reach scientific goals as well as goals related to licensing, partnering with industry or initiating clinical development programmes. Based on sets of guiding questions for different areas of target assessment, the GOT-IT framework is intended to stimulate academic scientists’ awareness of factors that make translational research more robust and efficient, and to facilitate academia–industry collaboration. Academic research has a key role in identifying new drug targets, but to lead to new drugs this research must progress to testing drug candidates in clinical trials, which are typically conducted by industry. This Perspective presents a framework to support academic scientists and funders in prioritizing target assessment activities and in defining a critical path to reach scientific goals as well as goals related to licensing, partnering with industry or initiating clinical trials.

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Improving target assessment in biomedical research: the GOT-IT recommendations.

The promise and perils of industry-funded science

Alzheimer's disease (AD) is a chronic neurodegenerative disease characterised by cognitive impairment, behavioural alteration, and functional decline. Over 130 AD-associated susceptibility loci have been identified by genome-wide association studies (GWAS), while whole genome sequencing (WGS) and whole exome sequencing (WES) studies have identified AD-associated rare variants. These variants are enriched in APOE, TREM2, CR1, CD33, CLU, BIN1, CD2AP, PILRA, SCIMP, PICALM, SORL1, SPI1, RIN3, and more genes. Given that aging is the single largest risk factor for late-onset AD (LOAD), the accumulation of somatic mutations in the brain and blood of AD patients have also been explored. Collectively, these genetic findings implicate the role of innate and adaptive immunity in LOAD pathogenesis and suggest that a systemic failure of cell-mediated amyloid-β (Aβ) clearance contributes to AD onset and progression. AD-associated variants are particularly enriched in myeloid-specific regulatory regions, implying that AD risk variants are likely to perturbate the expression of myeloid-specific AD-associated genes to interfere Aβ clearance. Defective phagocytosis, endocytosis, and autophagy may drive Aβ accumulation, which may be related to naturally-occurring antibodies to Aβ (Nabs-Aβ) produced by adaptive responses. Passive immunisation is providing efficiency in clearing Aβ and slowing cognitive decline, such as aducanumab, donanemab, and lecanemab (ban2401). Causation of AD by impairment of the innate immunity and treatment using the tools of adaptive immunity is emerging as a new paradigm for AD, but immunotherapy that boosts the innate immune functions of myeloid cells is highly expected to modulate disease progression at asymptomatic stage.

Genomics of Alzheimer's disease implicates the innate and adaptive immune systems.

Many companies have proprietary resources and/or data that are indispensable for research, and academics provide the creative fuel for much early-stage research that leads to industrial innovation. It is essential to the health of the research enterprise that collaborations between industrial and university researchers flourish. This system of collaboration is under strain. Financial motivations driving product development have led to concerns that industry-sponsored research comes at the expense of transparency ( 1 ). Yet many industry researchers distrust quality control in academia ( 2 ) and question whether academics value reproducibility as much as rapid publication. Cultural differences between industry and academia can create or increase difficulties in reproducing research findings. We discuss key aspects of this problem that industry-academia collaborations must address and for which other stakeholders, from funding agencies to journals, can provide leadership and support.

https://science.sciencemag.org/content/sci/357/6353/759.full.pdf

K. Noonan

Papers

Fostering reproducibility in industry-academia research