We have some exciting news. The AKU Society has just been awarded a £60,000 grant from the Childwick Trust. This will fund a research study into children with AKU, called SOFIA-Paediatric (‘Subchondral Ochronotic Features in Alkaptonuria in the paediatric age group’).

As many of you already know, there is a drug called nitisinone. We believe it treats AKU. It is being tested in the DevelopAKUre clinical trials, which finish next year. However, nitisinone does have side-effects. It stops the breakdown of an amino acid called tyrosine, contained in the protein that we eat. Tyrosine builds up in the body. In a very few cases, this may lead to eye problems, skin rash and impaired brain function. We need a very good reason before we start using it on children.

A study called SOFIA in 2017 observed how AKU affected adults. It showed that, although AKU only severely affects quality of life in early adulthood, people as young as 16 display the symptoms of AKU. A toxic acid – homogentisic acid – reaches very high levels in the blood, a dark colour appears in the eyes and ears and the way people walk changes. This new study will look at children under 16 to find out the exact age at which the damage starts. When we know this, we will know the best age to give children nitisinone.

In particular, we want to find out the age at which a damaging process called ochronosis begins in children. In AKU, some of the acid which builds up in the blood eventually ends up in tissue as a black substance. This substance makes bones and cartilage black and brittle, causing early onset osteoarthritis in joints. It can also build up in the heart, causing heart disease.

Fifteen children with AKU aged between five and 16 will take part in the study. Each child will make five visits with their parents over six years to research sites in London, Manchester, Birmingham and Liverpool. The visits will each take two days and the AKU Society will make sure they run smoothly. We will also recruit fifteen children without AKU, so that we have benchmarks against which to measure if and how AKU affects patients.

At the research sites, researchers will observe if and how AKU affects the body through magnetic resonance imaging (MRI) scans of the spine and joints. These will look at cartilage to see whether it has been damaged by ochronosis. They will also take photographs of children’s eyes and ears to see if they show the dark colouring caused by AKU. Meanwhile, they will collect blood and urine in order to test them for the genes linked with AKU.

New technology now allows scientists to look at ochronosis in ears by using laser light. This is called Raman spectroscopy – it was mentioned by Dr. Jemma Kerns at our last patient workshop, and you can see the presentation here. In addition, the study will include gait analysis. The researchers will attach reflective markers to parts of the body, then film them. They will then be able to model how the children walk on a computer and see if this has been affected by AKU. Although most research will happen at the nearest research sites, all children will travel to Liverpool with their parents for gait analysis and ear examination. We are now able to pay for this.

Finally, we also hope to make this an international study. There is a doctor in Poland who knows of ten children with AKU. Researchers in France, Slovakia and Maryland, USA, are also keen to take part. We therefore need to get funding for research in these countries. The bigger this study is, the stronger our evidence will be – and the more we will be able eventually to help children with AKU.