Hunter syndrome: improving gene therapy for this rare and devastating disease

Hunter syndrome, also called mucopolysaccharidosis type II, is a rare genetic disease that affects many organs and tissues in the body and almost exclusively affects boys. Caused by the lack of an enzyme that breaks down complex sugars in the body, a child’s symptoms will get worse over time. Although treatments are available that aim to replace the missing enzyme, it is difficult to get these into the brain. Professor Brian Bigger of the University of Manchester is aiming to improve the effectiveness of a stem cell gene therapy approach, offering new hope for children and their families affected by this devastating disease.

This project is jointly funded by Action Medical Research and LifeArc.

How are children’s lives affected now?

In Hunter syndrome, a faulty gene leads to a deficiency of an enzyme called iduronate-2-sulfatase (IDS), which breaks down large sugars. This leads to an abnormal accumulation of these large molecules in the child’s body, causing a wide range of symptoms affecting many tissues and organs – including their brain, liver, lungs, bones, eyes, skin and heart. Sadly, their lives will often be cut tragically short.

“A child with the most severe form of the condition will usually start to experience symptoms between two and four years of age,” says Professor Bigger. “They will have progressive learning difficulties and behavioural problems due to a build-up of complex sugars in their brain.”

Although therapies that aim to replace the faulty enzyme can be effective at treating some symptoms, the blood-brain-barrier prevents these treatments from crossing into the brain efficiently.

“There is an urgent need to develop better treatments for boys with this devastating condition – especially those that can reach inside the brain,” says Professor Bigger.

How could this research help?

“Our aim is to improve the effectiveness of our innovative stem cell gene therapy at getting the enzyme into the brain in patients with Hunter syndrome,” says Professor Bigger.

Professor Bigger’s team previously developed the approach that involves taking stem cells from bone marrow, inserting a correct copy of the IDS gene, and then transplanting them into the body. These cells then produce the IDS enzyme, treating the symptoms of the disease.

“Unfortunately, we’ve so far struggled to have much of an impact on brain symptoms as we can’t get high enough levels of the enzyme into these cells,” says Professor Bigger.

The researchers are now investigating if they can boost the levels of the enzyme in the brain by adding on a small protein tag that helps it to cross the blood-brain-barrier.

“If we can show this approach is both safe and effective, this laboratory research could help pave the way for a future clinical trial in boys with Hunter syndrome,” says Professor Bigger.

We do not provide medical advice. If you would like more information about a condition or would like to talk to someone about your health, contact NHS Choices or speak to your GP.