PhD Scholarship: Are there any long-term effects of being a Sanfilippo carrier?
The Sanfilippo Children’s Foundation is proud to be providing a supplementary scholarship to Nazzmer Nazri, who is undertaking a PhD project on Sanfilippo at The University of Adelaide, under the guidance of A/Prof Kim Hemsley (Flinders University) and Dr Nicholas Smith (Women’s and Children’s Hospital, Adelaide).
It is currently thought that carriers of Sanfilippo syndrome – those that possess only one faulty gene – are not affected. However, for some other similar diseases, there are studies linking carrier status with a higher than average risk of developing late-onset neurodegenerative disease. One example is Gaucher’s disease, in which carriers of the condition have an increased risk of developing Parkinson’s Disease later on in life.
Nazzmer’s PhD project, which is now into its second year, aims to investigate the impact of being a Sanfilippo carrier on the brain. Nazzmer will use mice that are carriers for Sanfilippo Type A and study their brain structure and function over time. Although the results are not directly transferrable to human Sanfilippo carriers, they could pave the way for further investigations exploring any potential risks and possible prevention methods.
Project Update
In 2020, the Sanfilippo Children’s Foundation provided a supplementary top-up scholarship to Nazzmer Nazri, a PhD student who undertook his PhD project at The University of Adelaide, under the mentorship and guidance of Professor Kim Hemsley (Flinders University, Adelaide) and Dr Nicholas Smith (Women’s and Children’s Hospital, Adelaide). Nazzmer’s PhD research project endeavoured to define the impact of being a carrier of a mutation associated with Sanfilippo syndrome (MPS IIIA).
Historically, carriers – those that possess only one functional copy of a lysosomal gene – have been thought to not be affected in any way. However, recent studies in other similar diseases have established a link between carrier status and neurodegeneration, where carriers are more susceptible to developing late-onset neurodegenerative disease compared to individuals with two functional copies of the gene. An example of this is Gaucher’s disease, where GBA mutation carriers have an increased risk of developing Parkinson’s Disease later in life.
Project outcomes
In this project, Nazzmer utilised mice that are carriers of a mutation in the sulfamidase gene and assessed them for changes in protein expression, neuronal architecture, and neuronal function.
Nazzmer found that whilst the structure of a particular type of neuron was not changed in carrier mice, protein levels in a few specific biological pathways were dysregulated in the cerebral cortex of carrier mice. The latter findings will be explored further within the group in the future.
As the experiments were performed in a mouse model, the results from this study need to be interpreted with caution for translatability to human Sanfilippo mutation carriers.
We look forward to bringing you the published results of Nazzmer’s studies as soon as they are available and are excited to see where Nazzmer’s career will take him next.
Project Summary
- Project title: Defining the neuropathological impact of heterozygosity in the gene encoding sulfamidase, a lysosomal degradative enzyme.
- Chief investigator: Nazzmer Nazri’s PhD project was carried out under the guidance of A/Prof Kim Hemsley at Flinders University and Dr Nicholas Smith at the Women’s and Children’s Hospital, Adelaide.
- Amount: $10,000 over 2 years
- Location: The University of Adelaide, Adelaide, Australia
- Status: Completed
