Can measuring the brain help clinical trials for Sanfilippo?

03 Jun 2021

Clinical trials to test potential therapies for Sanfilippo syndrome rely on accurate ways to measure whether the treatment is working.

Cognitive, neuropsychological and behavioural tests are used at the moment. They give vital information on the child’s development and how it compares to the typical development seen in children without Sanfilippo. However, these tests can sometimes be very difficult to complete, particularly for children with the challenging behavioural symptoms of Sanfilippo.

For this reason, finding other, easy to measure, biomarkers is essential for Sanfilippo, both in the research lab and in the clinic.

Biomarkers are characteristics that show the presence or stage of disease, and change as the disease changes. Examples of biomarkers include molecules in blood and saliva, or structures seen in MRI images.

Recently published research suggests that brain MRIs may be a useful tool to judge if possible therapies can stop neurodegeneration in Sanfilippo. MRIs may allow doctors to assess the health and development of the brain without relying only on behavioural or cognitive tests. 

The researchers in Ohio, USA, carried out the study to better understand how MRI changes match with the symptoms and progression of Sanfilippo. The team recruited 25 patients with Sanfilippo types A or B, and followed patients over one year to see how MRIs changed with time.

When compared to MRIs of children without Sanfilippo, the researchers saw reductions in brain volume over time in specific parts of the brains of children with Sanfilippo. Reduced brain volume was seen in the cerebral cortex, the outermost part of the brain, and in some of the deeper parts of the brain responsible for tasks like reasoning and speech. The MRIs also showed a greater volume of other parts of the brain including the cerebellum at the back of the brain and the fluid-filled ventricles, the cavities inside the brain.

The changes in specific parts of the brain matched well with the cognitive and behavioural tests usually used to measure disease progression. This is a good sign that brain MRIs could be used as a fast and accurate way to measure disease progression and treatment effects in clinical trials.

The study was supported by funds from The Children's Medical Research Foundation - A Cure For Kirby (USA), The Sanfilippo Research Foundation (USA), The Sanfilippo Children's Research Foundation (Canada), NIH grants (USA) and a research fellowship from Cure Sanfilippo Foundation (USA).