Cure Sanfilippo Funds Work Into Genetic Modifiers of Disease Severity

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Cure Sanfilippo Foundation | Sanfilippo News | fruit fly model project | illustration of researcher in a lab

The Cure Sanfilippo Foundation is supporting a research project that aims to characterize fruit fly models of Sanfilippo syndrome type A, and to identify genes that affect disease development in these models.

The two-year study is being led by Trudy Mackay, PhD, a professor of genetics and biochemistry at Clemson University in South Carolina.

“Our team is excited about the potential for this project to lead to a greater understanding of why [Sanfilippo A] patient variants have such large effects on nervous system function, and the prospect of identifying loci [genes] that ameliorate these symptoms and lead to therapeutic treatments,” Mackay said in a press release.

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What Will Our Daughter Remember?

Sanfilippo syndrome is caused by genetic mutations that impair the body’s ability to break down a complex sugar molecule called heparan sulfate. Sanfilippo type A, the most common and generally most severe form of the disease, is specifically caused by mutations in a gene called SGSH. 

Due to these mutations, heparan sulfate builds to toxic levels, causing cellular damage. However, the specific biological mechanisms that drive this damage remain incompletely understood, limiting research into ways of effective treatment.

Previous work funded by the Cure Sanfilippo Foundation led to the creation of various fruit fly lines harboring Sanfilippo-causing mutations. The fruit fly (drosophila) is a useful laboratory model — they can be housed easily and cheaply, and their naturally short lifespan means that experiments can typically be done faster than in larger animal models. The fly genome mimics roughly 75% of the human genome, so these animals are commonly used for genetic studies.

In this new project, researchers will cross the Sanfilippo fly lines with 200 other fly lines with well-characterized genetics, creating Sanfilippo flies with various genetic backgrounds. The researchers will assess disease severity as well as gene expression levels, meaning the extent to which individual genes are “turned on or off.”

Their goal is to identify “non-Sanfilippo” genes that influence disease severity. The team will characterize the biochemical, behavioral, and disease-associated features of these genes, with a particular eye towards potential targets for treatment or biomarkers of disease progression.

While the initial project will focus on Sanfilippo A, this research is expected to pave the way for similar studies in disease types.