Research sheds light on brain health of Sanfilippo carriers

22 Mar 2021

Associate Professor Kim Hemsley and her team of researchers from South Australia have published research in mice that indicates that Sanfilippo carriers may not be at increased risk of adult-onset dementias or neurodegenerative conditions.

Who are Sanfilippo carriers?

In order for an individual to develop Sanfilippo syndrome, two copies of a defective gene must be inherited, one from each parent. People who have one healthy and one defective gene copy are called carriers. These carriers are generally healthy and don’t know they are a carrier (unless they have a child with Sanfilippo syndrome or have genetic testing).

While Sanfilippo affects 1 child in around 70,000 births, many more people are carriers of the disease. Using Sanfilippo type A as an example: around 1 in every 169 people in the general population is a carrier for Sanfilippo type A. More information about genetic risk and carrier screening can be found on our website.

Do Sanfilippo carriers have a greater risk of adult-onset dementia?

There is some evidence that carriers of diseases similar to Sanfilippo are predisposed to developing dementia or other neurodegenerative conditions later on in life. For example, carriers of Gaucher's disease have a greater risk of developing Parkinson’s Disease and/or having a more rapidly-progressing form of Parkinson’s.

Associate Professor Kim Hemsley led a study to examine whether there is a link between Sanfilippo carrier status and late-onset dementia in a type A mouse model. This involved a team of researchers from Flinders University, The University of Adelaide and the South Australian Health and Medical Research Institute (SAHMRI). 

The researchers compared mice that were carriers of the Sanfilippo type A gene to mice that were not carriers over their mid- and late-life stages for signs of Alzheimer’s, Parkinson’s and other neurodegenerative diseases. To do this, they looked at the behaviour of the mice, and their brain chemistry and structure.

In one test called the negative geotaxis test, which is used to look at body movement coordination, old carrier mice displayed slower response rates compared to non-carrier mice. However, other behavioural tests showed no significant differences between the carrier and non-carrier mice at any age.

As expected, the researchers found that the carrier’s levels of the type A enzyme, sulfamidase, were 50% of the levels in the non-carrier mice. This level of the enzyme was sufficient to remove heparan sulfate in the carrier mice, with no heparan sulfate accumulation seen. There were no overall changes in important brain signalling chemicals between the two groups, including dopamine, which is affected in Parkinson’s.

While the researchers noted very subtle changes in the carrier mice in specific brain cells involved in a region of the brain to do with movement, they could not identify any features of the common neurodegenerative disorders. For example, no inclusion bodies or toxic plaques were observed.

Overall, while they could not rule out the possibility, the team concluded that the carrier mice did not appear to have any rapidly-progressing neurological decline with age.

Where to now?

These initial results are good news for Sanfilippo carriers, and further studies will be done to further understand the brain health of Sanfilippo carriers. Nazzmer Nazri, a co-author on the study and a PhD student in the Childhood Dementia Research Group at Flinders University, is continuing this work, with a top-up scholarship granted by the Foundation.

Information on genetic risk and how to get carrier testing is available on the Sanfilippo Children’s Foundation website here.