This project is jointly funded by Action Medical Research and Action for A-T.

How are children’s lives affected now?

Children with A-T have changes in a gene called ATM, which contains the instructions for making a protein called ATM that helps protect cells from damage – causing a range of symptoms that usually begin in early childhood and get worse over time.

“A child will usually develop symptoms caused by progressive nerve damage in part of the brain that controls balance and coordination. Most will need to use a wheelchair before their teens,” says Professor Horvath. “They will also have a weakened immune system and an increased risk of cancer – and sadly, most will have shortened lives.” 

One promising treatment approach is antisense oligonucleotide (ASO) therapy, which uses small pieces of genetic material designed to target specific ATM changes. Researchers hope personalised ASOs could help restore enough working ATM protein in affected cells to slow symptoms in children with A-T.  

How could this research help?

“Our goal is to identify reliable biological markers* that can help assess new ASO treatments more accurately in children with A-T,” says Professor Horvath.

Building on their previous work, which identified several potentially useful blood-based markers, the team will now carry out experiments on two different types of nerve cell. The researchers will generate these cells from patient samples and grow them in the laboratory.

“We will look for markers that can provide a measure of disease progression and whether a treatment is working,” says Professor Horvath. “We will also test two promising ASOs to determine whether they can restore working ATM protein and improve the health and function of these cells without harmful effects.” 

The researchers hope to identify reliable markers that could be used in future clinical trials, while also establishing the safety and effectiveness of these gene-based therapies.

*Biological markers are measurable changes – such as the levels of particular proteins or other molecules – that can provide an indication of disease progression and the effects of treatment.