A certain type of antibiotic (the aminoglycosides, such as gentamicin, kanamycin and tobramycin), are used widely across the world to treat life-threatening bacterial infections, including tuberculosis. These drugs have a downside, however – some people treated with them develop irreversible, and often profound, hearing loss. As a result, they are used sparingly in high-income countries, often as a treatment of last resort – for example, to combat serious chest infections or sepsis. They are also used to protect premature babies from infections that their under-developed immune system cannot cope with. Aminoglycosides are effective against a wide range of bacteria, so they are well-suited to this, despite the associated risk of hearing loss.
Around 1 in 500 people have a mutation (change in the DNA sequence) in a specific gene called MT-RNR1. The mutation is known as m.1555A>G. This mutation is strongly linked to the development of profound hearing loss after even a single dose of aminoglycoside. Children with cystic fibrosis are often tested for this mutation, because at some point in their care, they will require treatment with an aminoglycoside. Knowing if they have the mutation helps doctors to minimise the risks to the children’s hearing. However, the testing isn’t appropriate for premature babies – they often have to be given antibiotics urgently, and doctors can’t wait the three days it currently takes to get the test results.
Developing a ‘point of care’ test for m.1555A>G
We awarded a £5,000 Flexi Grant to Professor William Newman, based at the University of Manchester, to develop a genetic test for the m.1555A>G mutation that could detect it quickly, and ultimately allow doctors to make the best decisions for premature babies who need antibiotic treatment. Professor Newman collaborated with Genedrive, a Manchester-based company, to use their technology to develop a ‘point of care’ testing device for m.1555A>G. A point of care test is one that can be carried out as someone is being treated in a clinic, or, if they’re in hospital, at their bedside. The goal of these tests is to provide accurate results within a very short time (often minutes), thus speeding up diagnosis and treatment.
With the funding we gave them, the researchers were able to successfully design a device which could test for the mutation in a saliva sample, and generate an accurate result (whether someone has the mutation or not) within 35 minutes. Based on these results, they applied to the National Institute for Health Research (NIHR), the research funding arm of the NHS, for an i4i (Invention for Innovation) grant to develop their new technology further. Their application was successful, with the NIHR granting them £900,000 to continue their work. With these funds, they hope to further develop their technology to make it suitable for routine clinical use, and to gain CE certification for their device (to show that it conforms with health, safety and environmental protection standards required for products sold within the European Economic Area). They also plan to undertake feasibility and acceptance studies to show that the test can be used clinically, and that people are willing to take the test or allow their baby to take the test. This work is needed before the test can be rolled out for clinical use across the NHS.
What does this mean?
This test could be used to test all premature babies who need antibiotic treatment for whether they have the m.1555A.G mutation. If they have the mutation, then doctors can treat them with different antibiotics, to help protect their hearing. Introducing this test could help to reduce the number of premature babies in the UK who lose their hearing after being treated with aminoglycosides each year (estimated to be, on average, 1 case per neonatal unit/year). The researchers hope that their test, once they have developed it so that it is high enough quality to be used in the clinic, should cost much less than standard testing.
This grant could ultimately lead to a transformation of clinical practice in the UK (and worldwide) to avoid preventable antibiotic-induced hearing loss. It is a great example of how a small amount of funding from us can turn into a significant investment from other, larger research funders, giving projects the kick-start they need to bring real benefit to people.
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