Connection Between Epigenome, Selective Mutability, Evolution, and Human Disease
Li, Harris et al., PLoS Genetics
Researchers at the Baylor College of Medicine and elsewhere propose a "connection between the epigenome, selective mutability, evolution, and human disease" based on the findings of their study on associations of structural mutability with germline DNA methylation and with non-allelic homologous recombination mediated by low-copy repeats. "Combined evidence from four human sperm methylome maps, human genome evolution, structural polymorphisms in the human population, and previous genomic and disease studies consistently points to a strong association of germline hypomethylation and genomic instability," the Baylor-led team writes.
LabCorp Expands HCV PGx Testing With New GenoSure NS3/4A Rx-Resistance Dx
LabCorp has begun offering nationwide its hepatitis C GenoSure NS3/4A assay, which is designed to identify NS3 and NS4A mutations and NS3-associated resistance to a pair of recently approved HCV protease inhibitors.
According to LabCorp, the nucleic acid-sequencing assay is "the first in a series" of HCV drug-resistance tests developed by Monogram Biosciences to help gastroenterologists and hepatologists clinically evaluate HCV direct-acting antiviral agents.
“We look forward to expanding our broad HCV assay portfolio to support the development and clinical application of additional DAAs … that target other distinct steps in the HCV replication cycle,” said Chris Petropoulos, the reference lab's vice president of Monogram R&D.
LabCorp acquired Monogram Biosciences in August 2009 for $107 million.
HCV GenoSure NS3/4A is currently available both for clinical-lab and clinical-trial testing exclusively through LabCorp and its Monogram Biosciences Center of Excellence.
Approximately 3.2 million people in the US and as many as 170 million people worldwide are infected with HCV. Since 2002, the standard of care for HCV infection in the US has been treatment with pegylated alpha-interferon and ribavirin.
But in May, FDA approved the first two DAAs, one made by Merck & Co. called Victrelis (boceprevir) and the other developed by Vertex Pharmaceuticals called Incivek (telaprevir).
The drugs are typically used in combination with pegylated alpha-interferon and ribavirin to treat patients infected with HCV genotype 1. However, clinical trials conducted to help the two drugs win approval found that some HCV variants contain mutations that reduced their efficacy.
HCV GenoSure NS3/4A was designed as an end-run against these mutations by analyzing the genetic sequence for the non-structural proteins NS3 and NS4A of HCV genotypes 1a and 1b that encode for an enzyme "essential" to viral replication," LabCorp said.
As a result, the assay detects mutations in NS3 and NS4A, identifying those associated with resistance to Victrelis and Incivek.
The potential success of the GenoSure assay is almost a foregone conclusion, at least according to LabCorp CEO David King, who touted the early success of another Monogram-developed HCV drug-response assay and suggested it to be a kind of market meter for the GenoSure.
During the lab's third-quarter 2010 conference call, King said Monogram's IL 28-B test, which interrogates a mutation linked with successful response to peginterferon alpha-based therapies, "has grown significantly" since it debuted one month earlier.
He also said the test has been a source of modest growth both in clinical testing and in LabCorp's clinical-trials business — the same two market segments for which the GenoSure is aimed.
"It's not huge, and at this point it's certainly not anything that would be material to revenue, but we've seen a very substantial growth in the number of clinicians who are ordering IL 28-B," King said at the time.
Another potential demand driver for LabCorp's clinical testing and clinical-trials business are recent recommendations developed by the HCV Drug Resistance Advisory Group that emphasize the value of resistance testing as a way to develop and clinically evaluate new HCV drug candidates.
"In HIV, the routine use of resistance testing to guide antiviral drug treatment is established in clinical practice," LabCorp said today. "In response to the recent and future availability of DAA agents, some experts anticipate that drug resistance testing will provide similar value to the clinical management of HCV infection."
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