Philanthropies as partners for drug development in public–private partnerships

Disease-focused philanthropic organizations play an increasing role in the strategy and conduct of biomedical research, with many focusing on drug development for specific diseases and patient populations. More and more theynot only provide resources and expertise, but also take active part managing the strategy and objectives of targeted research programs, using approaches such as venture philanthropy. Many also lead and participate in public–private partnerships. One example is the partnership between the Polycystic Kidney Disease (PKD) Foundation and the Critical Path Institute (C-Path) which brings together several pharmaceutical companies and academic institutions to developnew broadly-used biomarkers. Another case is the partnership between JDRF (formerly known as the Juvenile Diabetes Research Foundation) and the Innovative Medicines Initiative (IMI), involving financial support of the IMIDIA project (Innovative Medicines Initiative for Diabetes) which is focused on improving beta-cell function and identifying biomarkers for diabetes treatment monitoring. These examples show that in addition to providing financial support and expertise, philanthropic foundations are also in a unique position to coordinate the patient and research communities to enable and accelerate specific medicines development projects

Featured Articles Coalition Against Major Diseases/European Medicines Agency biomarker qualification of hippocampal volume for enrichment of clinical trials in predementia stages of Alzheimer's disease

Abstract Background: Regulatory qualification of a biomarker for a defined context of use provides scientifically robust assurances to sponsors and regulators that accelerate appropriate adoption of biomarkers into drug development. Methods: The Coalition Against Major Diseases submitted a dossier to the Scientific Advice Working Party of the European Medicines Agency requesting a qualification opinion on the use of hippocampal volume as a biomarker for enriching clinical trials in subjects with mild cognitive impairment, incorporating a scientific rationale, a literature review and a de novo analysis of Alzheimer's Disease Neuroimaging Initiative data

Cytokine Profiles of Severe Influenza Virus-Related Complications in Children

RationaleEffective immunomodulatory therapies for children with life-threatening “cytokine storm” triggered by acute influenza infection are lacking. Understanding the immune profiles of children progressing to severe lung injury and/or septic shock could provide insight into pathogenesis.ObjectivesTo compare the endotracheal and serum cytokine profiles of children with influenza-related critical illness and to identify their associations with severe influenza-associated complications.MethodsChildren with influenza-related critical illness were enrolled across 32 hospitals in development (N = 171) and validation (N = 73) cohorts (December 2008 through May 2016). Concentrations of 42 cytokines were measured in serum and endotracheal samples and clustered into modules of covarying cytokines. Relative concentrations of cytokines and cytokine modules were tested for associations with acute lung injury (ALI), shock requiring vasopressors, and death/ECMO.Measurements and main resultsModules of covarying cytokines were more significantly associated with disease severity than individual cytokines. In the development cohort, increased levels of a serum module containing IL6, IL8, IL10, IP10, GCSF, MCP1, and MIP1α [shock odds ratio (OR) = 3.37, family-wise error rate (FWER) p < 10−4], and decreased levels of a module containing EGF, FGF2, SCD40L, and PAI-1 (shock OR = 0.43, FWER p = 0.002), were both associated with ALI, shock, and death-ECMO independent of age and bacterial coinfection. Both of these associations were confirmed in the validation cohort. Endotracheal and serum cytokine associations differed markedly and were differentially associated with clinical outcomes.ConclusionWe identified strong positive and negative associations of cytokine modules with the most severe influenza-related complications in children, providing new insights into the pathogenesis of influenza-related critical illness in children. Effective therapies may need to target mediators of both inflammation and repair