Researchers test ‘the very premise of precision medicine,’ the future of trial design

By Maggie Lynch

- Last updated on GMT

(Image: Getty/pogonici)
(Image: Getty/pogonici)

Related tags psychiatrics Clinical trial Precision medicine Research Drug development Drug development process Patient centricity

A proof-of-concept study using patient-derived cells to test drug response in clinical trials demonstrates the benefits of precision medicine, movement to which is the future of study design, says researcher.

Eli Lilly, Icahn School of Medicine, and Sema4 released the results of a collaborative proof-of-concept study that demonstrated the effectiveness of patient-derived cells as an approach to assess drug response.

Per this collaborative study​, drug screening and transcriptome analysis were performed at the Ichan School of Medicine at Mount Sinai. The screening was completed with compounds provided by Eli Lilly, which funded the study in collaboration with Mount Sinai.

Kristen Brennard, associate professor at the Ichan School of Medicine at Mount Sinai told us, “We wanted to understand to what extent, if any, screening on a cell type relevant to disease and/or using genetic backgrounds known to be impacted by disease, resulted in differential drug response. We were testing the very premise of precision medicine.”

Brennard explained that in studies examining drug response, understanding a cell type and a patient’s genetic background is imperative. To maximize drug screening, she said it pays to use disease-relevant cells obtained from the patients.

“The future of trial design will be a movement towards precision medicine. Not all drugs will work on all patients. Predicting which patients will benefit from which drugs is the future of medicine,”​ Brennard said.

Antipsychotic drugs​ approved by the US Food and Drug Administration (FDA) all target the same dopamine receptor. However, the study states that two-thirds of individuals with schizophrenia have no response or only partial response to these dopamine receptor treatments.

In the study, the cells used were isolated from 12 individuals with a schizophrenia diagnosis as well as cells from 12 healthy individuals as controls. These isolated cells generated induced pluripotent stem cells that became neural progenitor cells; the cell type targeted for neuropsychiatric disorders.

“Eight were classical cancer cell screening lines. The remaining 24 were neural progenitor cells differentiated from stem cells that were reprogrammed from patients and controls,”​ said Brennard on the cell isolation process.

A series of assays from each of the cells were treated with 135 different small molecules that were selected based on the drugs’ predicted interaction with schizophrenia-related biology and gene activity.

Results showed that the patient-derived cells yielded more relevant information than the generic cells. Some of the drug candidates reversed the gene expression signatures associated with schizophrenia, according to the researchers.

Source: Nature Communications
DOI: 10.1038/s41467-018-06515-4
"Expression-based drug screening of neural progenitor cells from individuals with schizophrenia​"
Authors: B. Readhead, B. Hartley, B. Eastwood, D. Collier, D. Evans, R. Farias, C. He, G. Hoffman, P. Sklar, J. Dudley, E. Schadt, R. Savić and K. Brennand

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