The gastrointestinal (GI) tract is the system of organs by which food is ingested and digested, nutrients are absorbed, and waste products are eliminated. GI cell proliferation is essential for maintaining normal physiological function and integrity of the protective epithelial barrier, however, as many GI cells turn over at a rapid rate, normal function and barrier maintenance are highly sensitive to toxic insults. When drug-induced GI toxicity occurs, either by cytotoxicity, inhibition of cell proliferation, or adverse pharmacological effect on receptors and enzymes, damage manifests with a variety of clinical symptoms including nausea, vomiting, ulceration, and diarrhea. It is essential to understand and minimize these consequences, thus AstraZeneca seeks a translationally relevant in vitro model to investigate gastrointestinal toxicity onset and recovery.
This is a Reduction-to-Practice Challenge that requires written documentation, experimental proof-of-concept data, and validation results.
Source: InnoCentive Challenge ID: 9933828
AstraZeneca Challenge: Robust Online In Vivo Measurement of Biomarker Concentrations
Health care is moving towards smart online devices such as wearables with smart phone apps for monitoring. In the same way that a Fitbit measures activity, people are now able to observe their heart rate and respiratory rate throughout the day. This InnoCentive Challenge attempts to harness the excitement around the technology of online monitoring and apply this technology to drug research and development. Our aspirations include measuring drug concentrations and markers of drug efficacy and toxicity. Such online longitudinal measurement of small molecules (e.g. testosterone, estrogens, corticosteroids, and acetaminophen) has the potential to impact the way that pharmacology and toxicology is investigated in preclinical drug discovery. The advantage would be to gain much more information from each experiment. Current studies, both preclinically and in our patients, are restricted by access to tissue biopsies, timing of such biopsies, and limitation on blood draws. There are already examples of online monitoring sensors for specific molecules, such as glucose, being used in the clinic to great effect. We want to access a generic device that can allow longitudinal measurement of the concentrations of multiple small molecules in blood and other tissues.
This is an electronic Request-for-Partners (eRFP) Challenge; the Solver will only need to submit a written proposal to be evaluated by the Seeker with the goal of establishing a collaborative partnership.
Source: InnoCentive Challenge ID: 9933932
The majority of all cases of chronic kidney disease, a key research area within AstraZeneca, originate in the glomerulus when filtration barrier function is compromised. However, a detailed cellular understanding of the functioning and pathology of the glomerulus has been limited by the lack of good in vitro models of glomerular function.
AstraZeneca is looking for approaches to develop a glomerular model system. Ideally, the in vitro model should incorporate a self-contained microphysiological unit where biologically appropriate media, fluid flow and shear stress can be modulated to simulate in vivo properties that will ultimately recapitulate the conditions necessary for endothelial and podocyte cell types to form a functional glomerular filtration barrier.
This is an ideation challenge and only requires a written solution.
Source: InnoCentive Challenge ID: 9933748
The proximal tubule, a part of the kidney nephron (the functional unit of the kidney), has highly specialized properties to do with the salvage and excretion of various compounds, salts and minerals that are very important to the body and would otherwise be lost in the urine. In addition, the proximal tubule is essential for the handling of many drugs and so-called xenobiotics that come from outside the body and from the environment (e.g., many artificial substances, including potential toxins). However, there are no good human models in vitro that can recapitulate and reproduce the function of the proximal tubule. A robust model for the proximal tubule is needed, especially since the proximal tubule has an essential role in drug clearance, because it is highly susceptible to damage in many kidney diseases, and it is also a target for drug-drug interactions and drug toxicity. Development of a proximal tubule model system in vitro could help to address some of the gaps in laboratory models for the study of kidney disease, toxicity, and drug handling.
AstraZeneca is seeking innovative approaches to developing a model system of the proximal tubule in vitro. Ideally, the model should incorporate a self-contained microphysiological unit in which biologically appropriate media, fluid flow, and shear stress can be modulated to reproduce the properties of the proximal tubule in vivo and ultimately recapitulate the structural and cellular conditions necessary for integrated proximal tubular function.
Source: InnoCentive Challenge ID: 9933749
Pancreatic islet beta-cells sense blood sugar levels and secrete insulin to maintain homeostasis. In patients with diabetes, islet beta-cells are either lacking or ineffective. Islet transplantation is a treatment strategy that allows diabetics to reduce or eliminate the need for insulin injections to control their disease. AstraZeneca is searching for a simple device to transplant human islets to facilitate testing of therapeutic agents.
This Challenge requires only a written proposal.
Source: InnoCentive Challenge ID: 9933735
AstraZeneca Challenge: Developing Clinically-Relevant Models for Diffuse Large B Cell Lymphoma (DLBCL)
Diffuse large B cell lymphoma (DLBCL) is the most common form of non-Hodgkin lymphoma and accounts for up to 30% of newly diagnosed cases in the United States. It is a heterogeneous disease which in part appears to be driven by chronic activation of key survival pathways. A limited number of DLBCL cell lines are available, however there are gaps, and specific patient subtypes are not represented. To add to the complexity of clinical diversity, new mutations are being identified in certain treatment-resistant patients. AstraZeneca is interested in innovative proposals to create suitable preclinical models of DLBCL.
This is a Reduction to Practice Challenge that requires a written proposal and experimental proof-of-concept data (and/or sample delivery).
The Challenge has a special award structure. Whether creating a model for DLBCL or a model of acquired resistance to ibrutinib, up to $10,000 will be designated for solutions that highlight novel technologies to generate in vitro cell lines, whereas up to $25,000 will be awarded for submissions that successfully utilize patient-derived tissues.
Source: InnoCentive Challenge ID: 9933016
Drug metabolism is the enzymatic process by which the body modifies pharmaceutical substrates. The liver is primarily responsible for reactions which convert lipid-soluble compounds into water-soluble metabolites that can easily be excreted by the kidney. Occasionally, these metabolites exhibit chemically reactivity towards host proteins, leading to inappropriate binding that may result in adverse drug reactions. AstraZeneca desires an innovative approach for the quantitative measurement of covalent binding to cellular proteins.
Source: InnoCentive Challenge ID: 9933662
Solid dosage forms (e.g. tablets) are the preferred dosage unit for pharmaceutical products. These units are produced by compressing particulate formulations. A major problem in the high speed pressing of tablet formulations of pharmaceutical API’s (Active Pharmaceutical Ingredient) is they sometimes tend to stick to the punches during the compression process. This causes weight loss defects in the tablets and thus costly manufacturing defects during production. A model is required to predict sticking of formulations in high speed presses to prevent losses in production.
This is an Ideation Challenge with a guaranteed award for at least one submitted solution.
Source: InnoCentive Challenge ID: 9933670
Screening compounds for undesirable effects on the heart or blood vessels is a key step in drug discovery and development, ideally performed by using predictive in vitro assays. Cardiac and vascular spheroids are a new type of assay that, despite showing great promise, are not the finished article. Hence the Seeker to this Challenge is looking for a novel approach to improve these assays. Particularly, the Seeker is interested in solutions that provide a core for the spheroids that senses and reports pressure.
Source: InnoCentive Challenge ID: 9933661
Oligonucleotide therapy is an emerging treatment option for various diseases. Binding of these short chain sequences to complimentary RNA can result in the decrease of certain gene products leading to a therapeutic effect. With specific targeting, the activity of these oligonucleotides could be improved by having a direct effect on tumor cells and other cell types associated with cardiovascular and metabolic diseases.
AstraZeneca is searching for a novel, platform technology to facilitate the selective delivery of short chain oligonucleotides. AstraZeneca intends to make up to 10 awards from a total award pool of up to $100,000 – awarded solutions will be advanced to produce proof of concept data in a subsequent Reduction to Practice challenge with milestone awards of up to $20,000 and a final award of up to $100,000. This second Challenge may be public or by invitation only.
Source: InnoCentive Challenge ID: 9933013