Fast onset drusen model for dry AMD
Using novel fast onset cellular models, how would you propose to recapitulate drusen formation in the early stages of dry age-related macular degeneration?
Seba Almedawar
Principal Scientist
Boehringer Ingelheim
All incoming answers accompanied by a collaboration proposal will be evaluated by a scientific jury, and, upon selection, chosen proposals are pursued through a joint collaboration with the successful applicants. Initial funding of up to 200,000 euros will be available for proposals that will receive support by our review team.
More information
The dry form of age-related macular degeneration (dry AMD) is the leading cause of blindness in older adults with more than 170 million individuals affected globally and a high unmet medical need. It is characterized by a slow deterioration of the cells of the macula that causes progressive vision loss eventually leading to blindness1.
One prominent aspect of the early pathology is the accumulation of yellowish extracellular deposits, so-called drusen, beneath the retinal pigment epithelium (RPE) over time. Sub-RPE drusen are mainly composed of lipids, apolipoproteins and complement components2 and their formation is a pathological manifestation shared by many other macular degenerative diseases beyond dry AMD. Drusen prevents the essential metabolic and oxygen exchange between the RPE and the blood stream, thus causing RPE and retinal atrophy. It is hypothesized that the clearance of drusen in dry AMD patients might improve the retinal condition and stop/slow-down disease progression1.
One challenge in the development of new therapeutic concepts targeting this aspect of the disease is the lack of fast onset and robust in vitro / ex vivo models. The currently described cellular models that aim at reproducing drusen have a very slow onset (>3 months in vitro3 and > 8 months in vivo4) or may lack quantitative and reproducible readouts5. Thus, such models have not proven feasible for routine testing of new therapeutic concepts in a preclinical (pharmaceutical) setting.
Therefore, new robust cellular in vitro or ex vivo models that recapitulate these early aspects of the disease in a foreseeable time frame may help us to develop new therapeutic options for dry AMD.
- Robust in vitro / ex vivo drusen model that is fast, reproducible, and quantitative
- in vitro model established in human primary/iPSC based RPE validated across different donors
- Ex vivo model based on animal derived tissues (e.g., mouse, rat, porcine, bovine, rabbit)
The following will be considered out of scope:
- Pure in vivo based models
- Slow onset drusen model (beyond one month-not including the RPE differentiation time)
If your project is selected, you will have the opportunity to directly collaborate with the Retinopathies Discovery Research team of Boehringer Ingelheim. You can expect appropriate funding for the prospective collaboration period. Your exact funding request should be outlined in your proposal. As a framework, we suggest that your initial funding request is structured in milestone and does not exceed 200,000 euros per submitted project in total.
The opportunity for a funded stay at Boehringer Ingelheim for technology exchange / training is potentially available, as is the availability of custom biological tools and reagents.
Our collaboration agreement will provide full transparency about each partner’s rights & obligations (including intellectual property rights). As part of the agreement, you will be encouraged to publish following the collaboration agreement (to be negotiated in good faith).
To maintain the highest degree possible in an open innovation environment, we plan to announce the winner(s) publicly and feature them on opnMe.com and our social media channels. We would guide you through this process and as part of it we would kindly ask for your upfront consent, in case our scientific jury has selected your answer.
We are seeking research collaboration proposals that contain:
- A well-structured proposal outlining a new and compelling scientific approach.
- Outlining of the technical feasibility, and potentially existing data or previous publications that support feasibility / experience with outlined technology, based on existing techniques and established assays.
- Your exact funding request should be outlined in your proposal based on a well-thought-through project. The project should be structured in milestones and planned with key decision points (clear Go/No-Go criteria). The funding request for the initial milestones resulting in a Go/No-Go decision should not exceed 200,000 euros per submitted project in total.
- Proven track record in the required field of expertise.
- Ability to implement the outlined solution as part of a scientific collaboration project with Boehringer Ingelheim including access to a laboratory.
Please use our answer submission template to provide a 2-3 page non-confidential proposal (available for download here).
If confidential data exists that would strengthen the proposal, please indicate that information is available to share under a Confidential Disclosure Agreement (CDA). If we find the non-confidential concept proposal sufficiently interesting, we will execute a CDA for confidential discussions.
We are currently seeking answers for the following scientific challenge: Using novel fast onset cellular models, how would you propose to recapitulate drusen formation in the early stages of dry age-related macular degeneration?
All incoming answers accompanied by a collaboration proposal will be evaluated by a scientific jury, and, upon selection, chosen proposals are pursued through a joint collaboration with the successful applicants. Initial funding of up to 200,000 euros will be available for each selected proposal.
Drusen in patient-derived hiPSC-RPE models of macular dystrophies
Galloway C. A., Dalvi S., Hung S. S. C., MacDonald L. A., Latchney L. R., Wong R. C. B., Guymer R. H., Mackey D. A., Williams D. S., Chung M. M., Gamm D. M., Pébay A., Hewitt A. W., Singh R.
Proc National Acad Sci 2017, 114, E8214–E8223.
Cell culture model that mimics drusen formation and triggers complement activation associated with age-related macular degeneration
Johnson L. V., Forest D. L., Banna C. D., Radeke C. M., Maloney M. A., Hu J., Spencer C. N., Walker A. M., Tsie M. S., Bok D., Radeke M. J., Anderson D. H.
Proc Natl Acad Sci U S A 2011, 108, 18277-82.
