Therapeutic Development in the Absence of Predictive Animal Models of Nervous System Disorders Proceedings of a Workshop (2017) / Chapter Skim
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3 Case Studies: Therapeutic Development for Parkinson's Disease and Schizophrenia in the Absence of Predictive Animal Models of Disease
3 Case Studies: Therapeutic Development for Parkinson's Disease and Schizophrenia in the Absence of Predictive Animal Models of Disease
Pages 15-22
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From page 15... ...
. • Academia and industry are collaborating to develop novel tools to support PD drug development, including various biomarkers, patient registries, natural history studies, induced pluripotent stem (iPS)
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From page 16... ...
The fact that the genetic and sporadic forms of the disease appear indistinguishable by clinical and pathological phenotype lends credence to the idea that both forms of the disease may arise from common biological pathways, he said. Importantly, LRRK2 is a kinase, making it an attractive, druggable target for pharmaceutical companies, who are experts in making selective kinase inhibitors, said Sherer.
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From page 17... ...
These questions will require studies in human patients, including natural history studies, said Egebjerg. MJFF has established patient registries and begun cohort studies of patients carrying the LRRK2 mutation, as well as individuals at risk of developing PD, in preparation for future clinical trials and to identify biomarkers that may be relevant to LRRK2 function.
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From page 18... ...
in human patients, most of the large-effect variants found so far cause constellations of symptoms, making the interpretation in animals more challenging; and (5) some of the strongest genetic risk factors identified appear to reflect relatively recent evolutionary events and thus are not shared with species other than primates.
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From page 19... ...
Research in polygenic disorders like schizophrenia therefore turns toward understanding the interaction of individual genetic risk factors on a network level rather than the impact of rare alleles alone. McCarroll said that lower costs for whole exome and genome sequencing have begun to allow scaling toward large cohorts, which may enable identification of variants in specific genes more strongly associated with schizophrenia (Singh et al., 2016)
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From page 20... ...
Such assayys, of couurse, require identifying i in ntermediate phhenotypes in the model syystem th hat are relevan nt to human disease. d TRANSLA ATING DISC COVERIES T TO TREATM MENTS Frrances Jensenn applauded the t use of annimal models to deconstruuct complex diseases into i componeent parts, butt noted that itt may be oveerreachinng to expect an a animal mo odel to providde a systems-llevel phenotyypic mimmic of human n disease.
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From page 21... ...
Egebjerg added that a similar type of deconstruction at the clinical level could also prove beneficial as a step toward identifying which patients might benefit from therapeutic approaches that target particular mechanisms. Frank Yocca concurred, noting that from a pharmaceutical industry perspective, there may be no choice but to find common components among very heterogeneous diseases.
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