This story has been updated from a previous version to include information about NIHR funding for the antibiotic-related hearing loss test.
The researchers will begin a feasibility study for the assay, which runs on Genedrive's PCR-based platform, this summer.
At the European Society of Human Genetics last weekend, the researchers explained that they will use the assay to identify neonatal patients with the m.1555A>G genotype. The mitochondrial mutation, which occurs in about 1 in 500 individuals, can cause ototoxicity in patients treated with gentamicin for sepsis. In infants with the mutation, irreversible hearing loss can occur if they receive the the antibiotic.
"We've known about the genetic change for around 25 years, but standard genetic testing takes about two to three days instead of almost right away," said William Newman, the corresponding author and associate professor of translational genomics at Manchester Center for Genomic Medicine, in an interview.
His team aimed to develop a point-of-care assay to identify the variant in a faster time frame for increased clinical utility. "The key in the neonatal setting is speeding the timing of the test and getting the result to treat newborns," Newman explained.
The researchers used buccal swabs collected from patients and ran the samples on the Genedrive device, performing asymmetric PCR amplification on the targeted DNA region where the mutation might exist — the section that codes the m.1555A>G mutation.
During the genotyping step, the targeted strands of the DNA will bind "more accurately, consistently, and effectively, if they're of the complementary genotype," Newman said.
He noted that if the mutations exist in the mitochondrial DNA sample, the sample will separate the strands during a denaturing step, where researchers heat the solution at different temperatures. While the wild-type DNA section elutes at 54° C, the mutation section instead elutes at 65° C, Newman said, adding that the temperature differential in the denaturing steps allows the researchers to collect DNA containing the mutation without bleeding or leakage from the wild-type gene that might occur.
According to Newman, the test had both a clinical sensitivity and specificity of 100 percent. "All the positive and negative controls we've tested have matched up when we've compared it against gold standard among different platform," he said. In future work Newman aims to reduce the time to diagnosis from the current 40 minutes.
Newman and his team will also work with Manchester, UK-based Genedrive, formerly known as Epistem, this summer to begin a multicenter feasibility study called "Development and Implementation of a Point-of-Care Pharmacogenetic Test to Avoid Antibiotic-Related Hearing Loss in Neonates."
Newman and his team's collaborators recently received £900,000 (about $1.2 million) of funding from the National Institute for Health Research for the multi-center project this summer. Newman said that his team will start implementing the study at the Manchester Hospital and an additional undisclosed center, which combined would treat more than 2,000 newborns a year.
He noted that the team will reach out to various neonatal centers across the UK in the next few years, with initial assay implementation starting in 2019. He declined to say how much a diagnostic test based on the technology would cost, but said he anticipates it would be "considerably cheaper than current approaches."
In addition, Newman's team aims to identify other opportunities in the point-of-care space, and explore whether their approach could be applied to different genetic conditions. They plan to file a patent for the assay after collecting validation data from the multicenter study.
Newman explained that his team has partnered with Genedrive because of the firm's past success in developing genomic assays and because both partners are located in Manchester. Genedrive has developed a portable, POC platform that performs a variety of genotyping tests including the mutation detection assay built by the Manchester researchers.
Newman's team is currently in talks with the firm regarding a commercialization strategy. However, he explained that "as IP discussion rolls out, we will need time to work out the details, and they are not set in stone at this time."
Newman said that his team "chose the neonatal [sector] first because we know that [providing gentamicin] is the recommended standard of care for babies [with infections] and that there's a large group of them," about 90,000 babies each year who could be saved from hearing loss if the group's test is used in the clinical setting.
He also plans on evaluating other patient groups who might be exposed to gentamicin and thus could also benefit from the assay.