lack of predictive animal models for neuropsychiatric diseases is arguably the
biggest single factor stifling drug development in the field. To kick-start
discovery for diseases such as autism, schizophrenia and depression,
stakeholders will need to abandon traditional models, build on emerging genetic
findings and capitalize on new capabilities in stem cell technology, imaging
and computational modeling.
The key opinion leaders agreed that the road to new models
starts with identifying genes that cause synaptic dysfunction. "Genetics
is the number-one stop," said Haas. "The genetic evidence for overlap
between diseases is highly compelling." Indeed, one of the few areas of neuropsychiatric
disease to see a surge of activity recently is large-scale genetic studies.
validity vs. construct validity
Nevertheless, the panelists said that the identification
of disease-associated genes offers the best chance so far for moving beyond the
face validity-based models that have held back drug development.
In addition to profiting from genomewide association
studies, the field stands to benefit from new technologies that generate
patient-derived induced pluripotent (iPS) cells, the panelists said. The
problem is in deciding what phenotypic changes at the cellular level can be
attributed to the cause of disease. In one notable case, Rett syndrome, there
is good agreement between cell culture and rodent models that allows drug
developers to rely on those systems for assaying candidate compounds.
looking at the effect of compounds on multiple brain regions is an important
extension of the new way of viewing these diseases as synaptic disorders, said
From imaging to the big picture
Bioinformatics, big data and large-scale collaborative
projects are perhaps the cornerstones of the next phase in translational
research for all areas of neurology.
Fishburn, C.S. & Osherovich, L. SciBX 7(31);
Published online Aug. 14, 2014
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AND INSTITUTIONS MENTIONED
New York, N.Y.
Biogen Idec Inc.
(NASDAQ:BIIB), Weston, Mass.
Boehringer Ingelheim GmbH, Ingelheim, Germany
Boston Children's Hospital, Boston, Mass.
Circuit Therapeutics Inc., Menlo Park, Calif.
Food and Drug Administration, Silver Spring, Md.
Harvard University, Cambridge, Mass.
Icahn School of Medicine at Mount Sinai, New York, N.Y.
Institute of Medicine, Washington D.C.
The Johns Hopkins University School of Medicine, Baltimore, Md.
Massachusetts Institute of Technology, Cambridge, Mass.
National Institutes of Health, Bethesda, Md.
Orion Bionetworks Inc., Cambridge, Mass.
Salk Institute for Biological Studies, La Jolla, Calif.