New study of kinder and more effective treatment for childhood dementia

The study, led by Professor Brian Bigger, will seek to improve the effectiveness of stem cell gene therapy to treat Hunter syndrome and Sanfilippo syndrome type B – two diseases caused by a genetic mutation that means the body can’t produce a vital enzyme, leading to fatal brain damage, and in the worst cases, a life expectancy of fifteen years.

The team will build on existing research led by Professor Bigger. In the earlier project, Bigger and his team treated the symptoms of Sanfilippo syndrome type A by taking stem cells from the bone marrow and delivering a correct copy of the faulty gene. They then transplanted the cells back into the body to produce the missing enzyme, which is essential for breaking down complex sugar molecules in the brain and nervous system. While this study led to clinical improvements for most patients, only a small proportion of the enzyme enters the brain, with the remainder delivered to the rest of the body. Additionally, the conditioning drugs required for a successful procedure – largely given in the form of chemotherapy - can be taxing for patients.

Now, the team plans to refine this gene therapy by exploring the use of gentler conditioning for the patient before stem cells are collected. Conditioning via chemotherapy is given to eliminate old stem cells and make room for modified cells – a lengthy process that can be physically and emotionally strenuous for the child and their family. The team will also increase the chance of success following treatment by using methods to help boost the level of enzyme reaching the brain.

There are few treatments currently available for these conditions — which affect around 300 children in the UK and are recognised as forms of childhood dementia — and no treatments exist that can slow down or reverse the impact on the brain. Children diagnosed with the diseases progressively lose motor skills such as walking and eating, miss developmental milestones and can present with behavioural issues.

If successful, this research could lead to a safe and long-lasting treatment for children with Hunter syndrome and Sanfilippo syndrome type B, allowing them to lead a long and healthy life. What’s more, it could pave the way for the development of similar gene therapies for other childhood dementias and potentially also adult dementias.

The study has been funded by the Great Ormond Street Hospital Children’s Charity’s (GOSH Charity) National Call – the largest UK-wide regular funding scheme dedicated to rare and complex paediatric disease research. Professor Bigger’s research is one of twelve projects which will this year benefit from £2.8million worth of funding awarded through GOSH Charity’s National Call – the most ever awarded via the scheme, due to the high standard of applications for this round of funding. The successful applicants, who are based at institutions across the UK, will investigate some of the rarest and most difficult to treat childhood diseases, with a view of unlocking breakthroughs in child medicine.