J. Pers. Med.2016, 6(1), 9; doi:10.3390/jpm6010009 - published 5 February 2016 Show/Hide Abstract
Abstract: This study aims to confirm the initial pharmacogenetic finding observed within the clinical proof-of-concept trial of an enhanced response to treatment with pomaglumetad methionil (LY2140023 monohydrate) in Caucasian schizophrenia patients homozygous for T/T at single nucleotide polymorphism rs7330461 in the serotonin (5-hydroxytryptamine) 2A receptor gene compared to A/A homozygous patients. The effect of the rs7330461 genotype on the response to pomaglumetad methionil treatment was assessed in three additional clinical trials and in an integrated analysis. Overall, this study includes data from 1115 Caucasian patients for whom genotyping information for rs7330461 was available, consisting of 513 A/A homozygous, 466 A/T heterozygous and 136 T/T homozygous patients. Caucasian T/T homozygous patients showed significantly (p ≤ 0.05) greater improvement in Positive and Negative Syndrome Scale (PANSS) total scores during treatment with pomaglumetad methionil 40 mg twice daily compared to A/A homozygous patients. Additionally, T/T homozygous patients receiving pomaglumetad methionil had significantly (p ≤ 0.05) greater improvements in PANSS total scores compared to placebo and similar improvements as T/T homozygous patients receiving standard-of-care (SOC) treatment. The findings reported here in conjunction with prior reports show that in Caucasian patients with schizophrenia, the T/T genotype at rs7330461 is consistently associated with an increased treatment response to pomaglumetad methionil compared to the A/A genotype.
J. Pers. Med.2016, 6(1), 8; doi:10.3390/jpm6010008 - published 27 January 2016 Show/Hide Abstract
Abstract: Over the last decade, the field of molecular diagnostics has undergone tremendous transformation, catalyzed by the clinical implementation of next generation sequencing (NGS). As technical capabilities are enhanced and current limitations are addressed, NGS is increasingly capable of detecting most variant types and will therefore continue to consolidate and simplify diagnostic testing. It is likely that genome sequencing will eventually serve as a universal first line test for disorders with a suspected genetic origin. Academic Medical Centers (AMCs), which have been at the forefront of this paradigm shift are now presented with challenges to keep up with increasing technical, bioinformatic and interpretive complexity of NGS-based tests in a highly competitive market. Additional complexity may arise from altered regulatory oversight, also triggered by the unprecedented scope of NGS-based testing, which requires new approaches. However, these challenges are balanced by unique opportunities, particularly at the interface between clinical and research operations, where AMCs can capitalize on access to cutting edge research environments and establish collaborations to facilitate rapid diagnostic innovation. This article reviews present and future challenges and opportunities for AMC associated molecular diagnostic laboratories from the perspective of the Partners HealthCare Laboratory for Molecular Medicine (LMM).
J. Pers. Med.2016, 6(1), 6; doi:10.3390/jpm6010006 - published 21 January 2016 Show/Hide Abstract
Abstract: The Biobank and Translational Genomics core at Partners Personalized Medicine requires robust software and hardware. This Information Technology (IT) infrastructure enables the storage and transfer of large amounts of data, drives efficiencies in the laboratory, maintains data integrity from the time of consent to the time that genomic data is distributed for research, and enables the management of complex genetic data. Here, we describe the functional components of the research IT infrastructure at Partners Personalized Medicine and how they integrate with existing clinical and research systems, review some of the ways in which this IT infrastructure maintains data integrity and security, and discuss some of the challenges inherent to building and maintaining such infrastructure.
J. Pers. Med.2016, 6(1), 4; doi:10.3390/jpm6010004 - published 20 January 2016 Show/Hide Abstract
Abstract: Academic medical centers require many interconnected systems to fully support genetic testing processes. We provide an overview of the end-to-end support that has been established surrounding a genetic testing laboratory within our environment, including both laboratory and clinician facing infrastructure. We explain key functions that we have found useful in the supporting systems. We also consider ways that this infrastructure could be enhanced to enable deeper assessment of genetic test results in both the laboratory and clinic.
J. Pers. Med.2016, 6(1), 5; doi:10.3390/jpm6010005 - published 20 January 2016 Show/Hide Abstract
Abstract: The integration of electronic medical records (EMRs) and genomic research has become a major component of efforts to advance personalized and precision medicine. The Electronic Medical Records and Genomics (eMERGE) network, initiated in 2007, is an NIH-funded consortium devoted to genomic discovery and implementation research by leveraging biorepositories linked to EMRs. In its most recent phase, eMERGE III, the network is focused on facilitating implementation of genomic medicine by detecting and disclosing rare pathogenic variants in clinically relevant genes. Partners Personalized Medicine (PPM) is a center dedicated to translating personalized medicine into clinical practice within Partners HealthCare. One component of the PPM is the Partners Healthcare Biobank, a biorepository comprising broadly consented DNA samples linked to the Partners longitudinal EMR. In 2015, PPM joined the eMERGE Phase III network. Here we describe the elements of the eMERGE clinical center at PPM, including plans for genomic discovery using EMR phenotypes, evaluation of rare variant penetrance and pleiotropy, and a novel randomized trial of the impact of returning genetic results to patients and clinicians.