Fibrosis in Crohn's disease can narrow the lumen of the intestine resulting in the need for surgical intervention. New medications are needed to address this unmet medical need.Credit: Shutterstock
Fibrosis occurs in many different diseases, affecting different organs. Whatever its cause, the outcome is the same: excessive deposition of extracellular matrix causing tissue stiffening, essentially, scarring. Fibrosis is often associated with chronic inflammation and aberrant wound healing, causing further health problems.
In complicated Crohn’s disease, for example, fibrosis can cause a narrowing of the intestine, leading to blockages. For these patients, surgical removal of a section of the intestine is currently the only effective treatment. However, symptoms often return because there is no cure for the underlying disease.
Therapeutics for Crohn’s disease, such as immuno-suppressants or biologics, can slow disease progression, but that is not enough. “We don't have anything that stops it,” says Elliott Klein, a senior principal scientist in Immunology & Respiratory Disease Research at Boehringer Ingelheim. “And we clearly don't have anything that reverses it.”
If there was a way to better model Crohn’s disease complications using cellular assays, that would go a long way towards finding such treatments, says Klein. The problem is that modelling such a complex disease is not a simple task. And solutions are likely to come from a wide group of researchers, some of whom may not even be aware that their expertise could help.
How do you go about solving a research question when you don’t know where the experts are? For this particular challenge, Klein has turned to opnMe.
Open questions
opnMe.com was launched two years ago as Boehringer Ingelheim’s bridge with external researchers. It started as a way of sharing chemical probes; molecules that had been carefully profiled but were no longer used in internal projects. Through opnMe.com, any researcher can request the probes, and approximately 3,500 compounds have already been shipped.
An open science platform is more than the compounds it offers, however. As director of the Structural Genomics Consortium, a non-profit organization that facilitates open science approaches to drug discovery, Aled Edwards has seen many molecule-sharing initiatives. Successful ones, he says, don’t just give away compounds, but also share all associated information. “The data are the treasure trove, not just the molecule.”
To ensure that opnMe includes that quality data, it is run by Boehringer Ingelheim’s scientists. “We carefully profile and document each compound,” says opnMe team leader Florian Montel, who is also a medicinal chemist. Boehringer Ingelheim researchers like Montel are also the first point of contact for opnMe’s users.
A few opnMe molecules are only available on a collaborative basis, determined by submission of innovative proposals. “It’s all about establishing a reliable framework for crowdsourcing,” says Adrian Carter, Global Head of Discovery Research Coordination at Boehringer Ingelheim, and opnMe mentor. “Crowdsourcing is about opening the innovation process and inviting contributions from the scientific community, to help solve research puzzles by providing tools or asking questions.”
From there, it was just a small step to opnMe’s current initiative, opn2EXPERTS, in which researchers are invited to submit proposals to solve research not linked to a specific compound.
One of the first questions on opn2EXPERTS is Klein’s, asking for suggestions to develop a cellular model for Crohn’s disease. Researchers with possible solutions can submit a proposal, which will be evaluated by Boehringer Ingelheim’s scientists to see if it could form the basis of a research collaboration (See 'Crowdsourcing process for biological questions').
“The goal is to establish a trusting and long-term relationship with these researchers,” explains Montel. Among the benefits for participating scientists are potential funding for the research project and access to Boehringer Ingelheim researchers and their drug discovery experience.
Now that his question is out there, Klein is waiting to see who will apply. Perhaps he’ll get responses from cell biologists or gastroenterologists, but maybe also from other scientific disciplines. He’s keeping an open mind, and says, “We'd be interested to hear from somebody who came in from left field. Who that would be, I am eager to find out.”
