Improving the Utility and Translation of Animal Models for Nervous System Disorders Workshop Summary (2013) / Chapter Skim
Currently Skimming:
6 Addressing the Translational Disconnect
6 Addressing the Translational Disconnect
Pages 55-66
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 55... ...
Hugo Geerts explained how quantitative systems pharmacology can be an effective translation tool, applying mathematical model-based decision support to drug development, and Thomas Steckler provided further 1 This selection of presentations are not intended to be a complete listing of all programs addressing translational issues for nervous system disorders.
|
From page 56... ...
DEVELOPING BETTER ANIMAL MODELS OF ETIOLOGY AND PATHOPHYSIOLOGY Richard Ransohoff, director of the Neuroinflammation Research Center at the Cleveland Clinic, discussed EAE and multiple sclerosis as a case example to illustrate some of the challenges in translating research from bedside to bench and back again. Multiple sclerosis is a chronic, inflammatory, demyelinating disease that is specific to humans.
|
From page 57... ...
There are also emerging models with unknown potential, such as transgenic mice with inducible oligodendrocyte cell death. Finally, a new mouse model of spontaneously developing EAE does recapitulate many of features of relapsingremitting multiple sclerosis (Berer et al., 2011)
|
From page 58... ...
Discussion of such facilities should consider whether spontaneous EAE models would also be housed there and whether there should also be contract facilities for demyelination/remyelination models, where accurate quantitative tissue analysis is critical. EFFORTS TO ADDRESS THE TRANSLATIONAL DISCONNECT Opportunities to Bring Researchers Together for Consensus Building Deanna Barch, professor of psychology, psychiatry, and radiology at Washington University, offered an illustration of what she called "the three-way problem" of linking basic and clinical science: The "basic animal researcher" studies spatial learning and memory using the Morris water maze.
|
From page 59... ...
Bringing Validated CNS Experimental Medicine Methods from Academia to Industry Seeing an opportunity to help bridge the gap between his clinical and preclinical colleagues, Gerry Dawson co-founded P1vital, 4 a clinical research organization focused on experimental medicine for central nervous system (CNS) disorders.
|
From page 60... ...
P1vital assembled an academic network of five UK academic institutions with expertise in CNS research (University of Oxford, Institute of Psychiatry London, University of Manchester, Cardiff University, and Imperial College London) , and a precompetitive consortium of five pharmaceutical companies that provided financial and practical support for the validation studies (AstraZeneca, GSK, Lundbeck, Organon [a Merck subsidiary]
|
From page 61... ...
Quantitative Systems Pharmacology as a Translational Tool Hugo Geerts, chief scientific officer for In Silico Biosciences, discussed quantitative systems pharmacology as a translational tool. To begin, he took stock of what the pharmaceutical industry could potentially learn from other successful industries, such as microelectronics and aeronautics.
|
From page 62... ...
A large amount of untapped clinical data exists for CNS drug development and a possible solution is an approach Geerts termed "computeraided research and development." This approach combines the best of the animal world with the clinical world, in an animal-independent implementation, he explained. One of the major issues in bridging the gap between biomarkers and clinical functioning is that in many cases, it is a very large jump from the individual biochemical change to the cognitive performance.
|
From page 63... ...
. To make this approach usable and actionable for pharmaceutical development, In Silico Biosciences leverages the preclinical data from academia over the past 60 years and integrates information on receptor physiology, CNS drug pharmacology, target exposure, human pathology, and imaging to create a computational neuropharmacology translational model bridging preclinical and clinical research.
|
From page 64... ...
genetics," is linked to WP04, "Cross-species and functional imaging models for drug discovery" to determine whether there are different activation patterns in patients depending on the CNVs they carry. Both are also linked to WP03, "Human cognitive testing," to the component of WP04 focused on rodent fMRI phenotyping, to WP01, "Linking animal and clinical models via electrophysiology," and to WP02, "Animal models of cognitive dysfunction that relate to clinical endpoints," as there are mouse models that carry these CNVs to be tested not only for behavior, but also electrophysiologically and via imaging.
|
From page 65... ...
The most significant threat, according to Steckler, is the instability of the pharmaceutical industry, with three pharmaceutical partners already opting out of the consortium because they decided to drop some or all of their psychiatry research programs. They may still provide expert input, but they are no longer actively generating data.
|
From page 66... ...
among EFPIA partners internal staff has to shoulder workload • Confidence building in internal strategy and processes • Risk to lose focus on internal projects (what works) • Initial budget estimation relatively inflexible; limited scope • Streamlining of processes, avoidance of error repetition for adjustments (not really an issue for NEWMEDS)
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.