New initiative to accelerate preclinical drug assays | AGÊNCIA FAPESP

New initiative to accelerate preclinical drug assays A proposal was presented by researchers affiliated with the Structural Genomics Consortium (SGC) in Nature Reviews Drug Discovery (image: release)

New initiative to accelerate preclinical drug assays

May 20, 2015

By Karina Toledo

Agência FAPESP – Accelerating the advance of basic science required to develop new drugs through partnerships among universities, governments and the pharmaceutical industry in an environment of open access to knowledge has been the principal objective of the Structural Genomics Consortium (SGC) in its ten years of existence.

The SGC now proposes to move its model of open-source patent-free collaboration to the next stage of the drug discovery process, which comprises preclinical trials with patient-derived cell and tissue samples, carried out in partnership with research laboratories. The idea was presented in a Comment published recently by the journal Nature Reviews Drug Discovery.

“The two main objectives of our initiative are to increase our understanding of the molecular bases of cancer and inflammatory diseases (as well as other diseases, as our network grows) and to identify specific targets for which pharmacological modulation ameliorates key disease phenotypes,” the authors wrote.

Among those who signed the Comment are two Brazilians, Katlin Brauer Massirer and Mário Henrique Bengtson, who are researchers at the University of Campinas (UNICAMP) in São Paulo State, Brazil and members of the SGC-linked center that was recently set up there with FAPESP’s support (read more at

“The idea is to continue the work already being performed by the SGC,” Massirer said. “The consortium’s current role is to develop molecules with the potential to become new drugs. The article sets out to show that even if biologically active compounds are found, there is still a long way to go until they can be tested in patients to assess their effectiveness.”

The SGC was founded in 2004 with the aim of promoting basic research in areas such as epigenetics that are considered high risk, for which it would be difficult to obtain funding by traditional methods. The initial focus was on studying genetic differences between human beings. Next, the group turned to studying the three-dimensional structure of biomedically relevant proteins, which could be targets for the development of new drugs.

Through collaboration by more than 300 research groups in 40 countries, as well as ten of the largest pharmaceutical companies and several not-for-profit research funding organizations, the SGC has produced structures for over 1,500 proteins implicated in the development of therapies against cancer, diabetes, obesity and psychiatric disorders.

In addition to the original hubs at the University of Toronto (Canada) and the University of Oxford (UK), the SGC added a team of Brazilian researchers at UNICAMP’s Protein Kinase Chemical Biology Center, supported by FAPESP through its Partnership for Technological Innovation Program (PITE), in 2015. The new lab is headed by Paulo Arruda, Full Professor of Genetics at UNICAMP’s Biology Institute.

Two new research lines were also added. One is the study of inhibitors for kinases (a class of enzymes) that control RNA splicing, an editing process by which molecules become mature and ready to encode proteins. The other line focuses on the discovery of target proteins to modulate the resistance of plants to water stress.

Creating shortcuts

According to Massirer, more than ten years of work may be required between the discovery of a molecule with pharmacological potential in the lab and its transformation into a drug for human use.

The goal for the new partnership proposed by the SGC is to accelerate this process and increase the success rate for candidate drugs in clinical trials, which is currently in the range of only 4%.

“One of the causes of the high failure rate is an inappropriate choice of initial drug target, “said Bill Zuercher, Senior Scientific Investigator, GlaxoSmithKline (GSK) Research & Development, at the unveiling of UNICAMP’s new center in March. “This isn’t an easy problem to solve. We need to advance our knowledge of fundamental biology, which is the type of research even a large organization like GSK cannot do on its own.”

Another aim of the new initiative is to attract research groups linked to the clinical field and hence with access to cell samples from patients with target diseases. “We’re going to use these cells in the lab to validate targets and increase the chances of success in future stages,” Massirer said.

The focus for several collaborative experiments will be on collecting cells from the skin of patients and reprogramming them to induce pluripotency. “This undifferentiated state enables cells to be directed in lab experiments to generate a specific lineage. For example, we can induce cardiomyocyte differentiation to understand the functioning of the heart,” she said.

In the article, the group stressed that all of the necessary ingredients for high-quality and relevant preclinical trials are rarely all found in the same institution.

“Industry usually has the most experience in the design and development of new chemicals or antibodies; the clinical academic community cares for the patients and provides deep disease expertise, and the academic research community customarily provides the molecular and technological insights necessary for mechanistic studies,” the authors wrote.

As it has always done in previous projects, the SGC is proposing collaboration among these three areas in a patent-free environment.

“The commitment to open-source research and data sharing is a key feature of this plan and is expected to accelerate the science, to make data generation more transparent and thus more reproducible, to reduce the costs and time associated with executing multi-institutional, multi-national and multi-sector collaborations, and to alleviate ethical concerns that might arise when commercial and scientific interests are juxtaposed with patient samples,” the authors concluded.

According to Bengtson, all of the research will be open access up to the identification of biologically active molecules and validation of therapeutic targets.

“From then on, any group that wants to invest and develop a product based on this knowledge can do so,” he said. “Finding a molecule that has the desired effect on cells or tissue is only one of the first steps in the drug discovery process. The molecule then typically must go through several alterations until it can be successfully tested in patients and approved for use. That process entails heavy investment by the pharmaceutical industry.”


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